tablets - pharmaceutics
TRANSCRIPT
TABLETSAseel Samaro
DefinitionDefinition according to the BPTablets are dosage forms that are circular in shape with either flat or convex faces and prepared by compressing the medicament or mixture of medicaments usually with added substances
Tablets are now the most popular dosage form ( 70 of all ethical pharmaceutical preparations produced)
Advantages of tablets1 Production aspect Large scale production at lowest cost Easiest and cheapest to package and ship High stability
2 User aspect (doctor pharmacist patient) Easy to handle Lightest and most compact Greatest dose precision and least variability Coating can mark unpleasant tastes and improve
patient acceptability
Disadvantages of tablets1 Some drugs resist compression into dense compact
2 Drugs with poor wetting slow dissolution intermediate to large dosages may be difficult or impossible to formulate amp manufacture as tablet that provide adequate or fill drug bioavailability
3 Bitter taste drugs drugs with an objectionable odor or sensitive to oxygen or moisture may require
Encapsulation or entrapment prior to compression or The tablets require coating
Tableting machine
DefinitionDefinition according to the BPTablets are dosage forms that are circular in shape with either flat or convex faces and prepared by compressing the medicament or mixture of medicaments usually with added substances
Tablets are now the most popular dosage form ( 70 of all ethical pharmaceutical preparations produced)
Advantages of tablets1 Production aspect Large scale production at lowest cost Easiest and cheapest to package and ship High stability
2 User aspect (doctor pharmacist patient) Easy to handle Lightest and most compact Greatest dose precision and least variability Coating can mark unpleasant tastes and improve
patient acceptability
Disadvantages of tablets1 Some drugs resist compression into dense compact
2 Drugs with poor wetting slow dissolution intermediate to large dosages may be difficult or impossible to formulate amp manufacture as tablet that provide adequate or fill drug bioavailability
3 Bitter taste drugs drugs with an objectionable odor or sensitive to oxygen or moisture may require
Encapsulation or entrapment prior to compression or The tablets require coating
Tableting machine
Advantages of tablets1 Production aspect Large scale production at lowest cost Easiest and cheapest to package and ship High stability
2 User aspect (doctor pharmacist patient) Easy to handle Lightest and most compact Greatest dose precision and least variability Coating can mark unpleasant tastes and improve
patient acceptability
Disadvantages of tablets1 Some drugs resist compression into dense compact
2 Drugs with poor wetting slow dissolution intermediate to large dosages may be difficult or impossible to formulate amp manufacture as tablet that provide adequate or fill drug bioavailability
3 Bitter taste drugs drugs with an objectionable odor or sensitive to oxygen or moisture may require
Encapsulation or entrapment prior to compression or The tablets require coating
Tableting machine
Disadvantages of tablets1 Some drugs resist compression into dense compact
2 Drugs with poor wetting slow dissolution intermediate to large dosages may be difficult or impossible to formulate amp manufacture as tablet that provide adequate or fill drug bioavailability
3 Bitter taste drugs drugs with an objectionable odor or sensitive to oxygen or moisture may require
Encapsulation or entrapment prior to compression or The tablets require coating
Tableting machine
Tableting machine
TYPES OF TABLETS 1 COMPRESSED TABLETS In addition to the medicinal agent or agents
compressed tablets usually contain a number of pharmaceutical adjuncts including the following
Diluents or fillers which add the necessary bulk to a formulation to prepare tablets of the desired size
Binders or adhesives which promote adhesion of the particles of the formulation allowing a granulation to be prepared and maintaining the integrity of the final tablet
Disintegrants or disintegrating agents which promote breakup of the tablets after administration to smaller particles for ready drug availability
Antiadherents glidants lubricants or lubricating
agents which enhance the flow of the material into the tablet dies minimize wear of the punches and dies prevent fill material from sticking to the punches and dies and produce tablets with a sheen
Miscellaneous adjuncts such as colorants and flavorants
After compression tablets may be coated with various materials as described later Tablets for oral buccal sublingual or vaginal administration may be prepared by compression
MULTIPLY COMPRESSED TABLETS
Multiply compressed tablets are prepared by subjecting the fill material to more than a single compression
The result may be a multiple-layer tablet or a tablet within a tablet the inner tablet being the core and the outer portion being the shell
Layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form two-layered or three- layered tablets depending on the number of separate fills
Each layer may contain a different medicinal agent separated for reasons of
1 chemical or physical incompatibility2 staged drug release3 for the unique appearance of the layered tablet
Usually each portion of fill is a different color to produce a distinctive-looking tablet
In preparation of tablets within tablets special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
TYPES OF TABLETS 1 COMPRESSED TABLETS In addition to the medicinal agent or agents
compressed tablets usually contain a number of pharmaceutical adjuncts including the following
Diluents or fillers which add the necessary bulk to a formulation to prepare tablets of the desired size
Binders or adhesives which promote adhesion of the particles of the formulation allowing a granulation to be prepared and maintaining the integrity of the final tablet
Disintegrants or disintegrating agents which promote breakup of the tablets after administration to smaller particles for ready drug availability
Antiadherents glidants lubricants or lubricating
agents which enhance the flow of the material into the tablet dies minimize wear of the punches and dies prevent fill material from sticking to the punches and dies and produce tablets with a sheen
Miscellaneous adjuncts such as colorants and flavorants
After compression tablets may be coated with various materials as described later Tablets for oral buccal sublingual or vaginal administration may be prepared by compression
MULTIPLY COMPRESSED TABLETS
Multiply compressed tablets are prepared by subjecting the fill material to more than a single compression
The result may be a multiple-layer tablet or a tablet within a tablet the inner tablet being the core and the outer portion being the shell
Layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form two-layered or three- layered tablets depending on the number of separate fills
Each layer may contain a different medicinal agent separated for reasons of
1 chemical or physical incompatibility2 staged drug release3 for the unique appearance of the layered tablet
Usually each portion of fill is a different color to produce a distinctive-looking tablet
In preparation of tablets within tablets special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Disintegrants or disintegrating agents which promote breakup of the tablets after administration to smaller particles for ready drug availability
Antiadherents glidants lubricants or lubricating
agents which enhance the flow of the material into the tablet dies minimize wear of the punches and dies prevent fill material from sticking to the punches and dies and produce tablets with a sheen
Miscellaneous adjuncts such as colorants and flavorants
After compression tablets may be coated with various materials as described later Tablets for oral buccal sublingual or vaginal administration may be prepared by compression
MULTIPLY COMPRESSED TABLETS
Multiply compressed tablets are prepared by subjecting the fill material to more than a single compression
The result may be a multiple-layer tablet or a tablet within a tablet the inner tablet being the core and the outer portion being the shell
Layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form two-layered or three- layered tablets depending on the number of separate fills
Each layer may contain a different medicinal agent separated for reasons of
1 chemical or physical incompatibility2 staged drug release3 for the unique appearance of the layered tablet
Usually each portion of fill is a different color to produce a distinctive-looking tablet
In preparation of tablets within tablets special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
MULTIPLY COMPRESSED TABLETS
Multiply compressed tablets are prepared by subjecting the fill material to more than a single compression
The result may be a multiple-layer tablet or a tablet within a tablet the inner tablet being the core and the outer portion being the shell
Layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form two-layered or three- layered tablets depending on the number of separate fills
Each layer may contain a different medicinal agent separated for reasons of
1 chemical or physical incompatibility2 staged drug release3 for the unique appearance of the layered tablet
Usually each portion of fill is a different color to produce a distinctive-looking tablet
In preparation of tablets within tablets special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form two-layered or three- layered tablets depending on the number of separate fills
Each layer may contain a different medicinal agent separated for reasons of
1 chemical or physical incompatibility2 staged drug release3 for the unique appearance of the layered tablet
Usually each portion of fill is a different color to produce a distinctive-looking tablet
In preparation of tablets within tablets special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
SUGARCOATED TABLETS Compressed tablets may be coated with a colored or
an uncolored sugar layer
The coating is water soluble and quickly dissolves after swallowing
1 The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor
2 The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturerrsquos information
Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size weight and shipping costs
Sugarcoating may add 50 to the weight and bulk of the uncoated tablet
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
FILM-COATED TABLETS Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like film
The film is usually colored and has the advantage over sugarcoatings in that it is
1 more durable2 less bulky3 less time- consuming to apply
By its composition the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
GELATIN-COATED TABLETS
A recent innovation is the gelatin-coated tablet
The innovator product the gelcap is a capsule- shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
ENTERIC-COATED TABLETS Enteric-coated tablets have delayed-
release features
They are designed to pass unchanged through the stomach to the intestines where the tablets disintegrate and allow drug dissolution and absorption andor effect
Enteric coatings are employed when the drug substance
is destroyed by gastric acid or is particularly irritating to the gastric
mucosa or when bypass of the stomach substantially
enhances drug absorption
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are flat oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
They enable oral absorption of drugs that are destroyed by the gastric juice andor are poorly absorbed from the gastrointestinal tract
Buccal tablets are designed to erode slowly whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base
They are intended to be slowly dissolved in the oral cavity usually for local effects although some are formulated for systemic absorption
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
CHEWABLE TABLETS Chewable tablets which have a
smooth rapid disintegration when chewed or allowed to dissolve in the mouth have a creamy base usually of specially flavored and colored mannitol
Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
EFFERVESCENT TABLETS Effervescent tablets are prepared
by compressing granular effervescent salts that release gas when in contact with water
These tablets generally contain medicinal substances that dissolve rapidly when added to water
The ldquobubble actionrdquo can assist in breaking up the tablets and enhancing the dissolution of the active drug
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
MOLDED TABLETS Certain tablets may be prepared by
molding rather than by compression The resultant tablets are very soft and soluble and are designed for rapid dissolution
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
TABLET TRITURATES Tablet triturates are small usually cylindrical molded or compressed
tablets containing small amounts of usually potent drugs
Today only a few tablet triturate products are available commercially with most of these produced by tablet compression
Since tablet triturates must be readily and completely soluble in water only a minimal amount of pressure is applied during their manufacture
A combination of sucrose and lactose is usually the diluent
The few tablet triturates that remain are used sublingually such as nitroglycerin tablets
Pharmacists also employ tablet triturates in compounding For example triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
HYPODERMIC TABLETS Hypodermic tablets are no longer available in the United States
They were originally used by physicians in extemporaneous preparation of parenteral solutions
The required number of tablets was dissolved in a suitable vehicle sterility attained and the injection performed
The tablets were a convenience since they could be easily carried in the physicianrsquos medicine bag and injections prepared to meet the needs of the individual patients
However the difficulty in achieving sterility and the availability of prefabricated injectable products some in disposable syringes have eliminated the need for hypodermic tablets
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
DISPENSING TABLETS Dispensing tablets are no longer in use
They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions they were not dispensed as such to the patient
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate and release their medication with no special rate-controlling features such as special coatings and other techniques
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-release tablets) are designed to release their medication in a predetermined manner over an extended period
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
VAGINAL TABLETS Vaginal tablets also called vaginal inserts are
uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects
They contain antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis antifungals for the treatment of vulvovaginitis
candidiasis caused by Candida albicans and related species
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS Instant-release tablets (rapidly dissolving tablets or RDTs) are
characterized by disintegrating or dissolving in the mouth within 1 minute some within 10 seconds
Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets
They liquefy on the tongue and the patient swallows the liquid
A number of techniques are used to prepare these tablets including Lyophilization soft direct compression
These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution They have the stability characteristics of other solid dosage forms
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The original fast-dissolving tablets were molded tablets for sublingual use
They generally consisted of active drug and lactose moistened with an alcoholndashwater mixture to form a paste
The tablets were then molded dried and packaged
For use they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin
Also they have been used for drugs that are destroyed in the gastrointestinal tract such as testosterone administered sublingually for absorption to minimize the first-pass effect
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
These RDTs are more convenient to carry and administer than an oral liquid
There are no standards that define an RDT but one possibility is dissolution in the mouth within approximately 15 to 30
seconds anything slower would not be categorized as rapidly dissolving
Packaging They are generally packaged in cards or bubble-type
packaging with each individual tablet in its own cavity
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Not withstanding these advantages there are a number of disadvantages and difficulties associated with formulating RDTs including
drug loading taste masking friability manufacturing costs stability of the product
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
COMPRESSED TABLETS The physical features of compressed tablets are well known Round oblong or unique in shape thick or thin large or small in diameter flat or convex unscored or scored in halves thirds or quadrants engraved or imprinted with an identifying symbol andor code
number coated or uncoated colored or uncolored one two or three layered
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablet diameters and shapes are determined by the die and punches used in compression
The less concave the punches the flatter the tablets conversely The more concave the punches the more convex the resulting
tablets
Punches with raised impressions produce recessed impressions on the tabletsPunches with recessed etchings produce tablets with raised impressions or monograms
Monograms may be placed on one or on both sides of a tablet depending on the punches
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets tablets must meet other physical specifications and quality standards
These include criteria for Weight Weight variation Content uniformity Thickness Hardness Disintegration Dissolution
These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
1 Tablet Weight and USP Weight Variation Test
The quantity of fill in the die of a tablet press determines the weight of the tablet
The volume of fill is adjusted with the first few tablets to yield the desired weight and content
For example if a tablet is to contain 20 mg of a drug substance and if 100000 tablets are to be produced 2000 g of drug is included in the formula
After the addition of the pharmaceutical additives such as the diluent disintegrant lubricant and binder the formulation may weigh 20 kg which means that each tablet must weigh 200 mg for 20 mg of drug to be present
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Thus the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg
During production sample tablets are periodically removed for visual inspection and automated physical measurement
The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets
In the test 10 tablets are weighed individually and the average weight is calculated
The tablets are assayed and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
2 Content Uniformity
By the USP method 10 dosage units are individually assayed for their content according to the method described in the individual monograph
Unless otherwise stated in the monograph the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85 to 115 of the label claim and the standard deviation is less than 6
If one or more dosage units do not meet these criteria additional tests as prescribed in the USP are required
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
3 Tablet Thickness
The thickness of a tablet is determined by1 The diameter of the die2 The amount of fill permitted to enter the die3 The compaction characteristics of the fill material4 The force or pressure applied during compression
To produce tablets of uniform thickness during and between batch productions for the same formulation care must be exercised to employ the same factors of fill die and pressure
The degree of pressure affects not only thickness but also hardness of the tablet hardness is perhaps the more important criterion since it can affect disintegration and dissolution
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
4 Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3000 and as much as 40000lb of force
In production of tablets Generally the greater the pressure applied the harder the tablets although the characteristics of the granulation also have a bearing on hardness
Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly are intentionally made hard other tablets such as those for immediate drug release are made soft
Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms pounds or in arbitrary units) required to break a tablet
A force of about 4kg is considered the minimum requirement for a satisfactory tablet
A tabletrsquos durability may be determined through the use of a friabilator
A maximum weight loss of not more than 1 generally is considered acceptable for most products
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
5 Tablet Disintegration For the medicinal agent in a tablet to become fully available for
absorption the tablet must first disintegrate and discharge the drug to the body fluids for dissolution
Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract
In these instances tablet disintegration provides drug particles with an increased surface area for activity within the gastrointestinal tract
All USP tablets must pass a test for disintegration which is conducted in vitro using a testing apparatus
The apparatus consists of a basket and rack assembly containing six open-ended transparent tubes of USP-specified dimensions held vertically upon a 10-mesh stainless steel wire screen
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablets must disintegrate within the times set in the individual monograph usually 30 minutes but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets
If one or more tablets fail to disintegrate additional tests prescribed by the USP must be performed
Enteric-coated tablets are similarly tested except that the tablets are tested in simulated gastric fluid for 1 hour after which no sign of disintegration cracking or softening must be seen
They are then actively immersed in the simulated intestinal fluid for the time stated in the individual monograph during which time the tablets disintegrate completely for a positive test
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
6 Tablet Dissolution In vitro dissolution testing of solid dosage forms is
important for a number of reasons
It guides formulation and product development toward product optimization
Dissolution studies in the early stages of a productrsquos development allow differentiation between formulations and correlations identified with in vivo bioavailability data
Consistent in vitro dissolution testing ensures bioequivalence from batch to batch
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable prediction of or correlation with the productrsquos
in vivo bioavailability
The system relates combinations of a drugrsquos solubility (high or low) and its intestinal permeability (high or low) as a possible basis for predicting the likelihood of achieving a successful in vivondashin vitro correlation (IVIVC)
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Using this system drugs are placed into one of four categories as follows
1 Category I drug (high-solubility and high-permeability)
2 Category II drug dissolution may be the rate-limiting step for absorption and an IVIVC may be expected - dissolution rate is slower than the rate of gastric emptying -
3 Category III drug (In the case of a high-solubility and low- permeability ) permeability is the rate-controlling step and only a limited IVIVC may be possible
4 Category IV drug (low solubility and low permeability) significant problems are likely for oral drug delivery
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablet disintegration is the important first step to the dissolution of the drug in a tablet
A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet including1 particle size of the drug substance2 solubility and hygroscopicity of the formulation3 type and concentration of the disintegrant4 binder5 lubricant6 manufacturing method7 particularly the compactness of the granulation8 compression force used in tableting9 any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods wet granulation dry granulation direct compression
Most powdered medicinal agents require addition of excipients such as
diluents binders disintegrants Lubricants to provide the desired characteristics for tablet manufacture and efficacious use
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper of the tablet press into the dies to enable high-speed compression of the powder mix into tablets
Granulations of powders provide this free flow
Granulations also increase material density improving powder compressibility during tablet formation
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Reasons for Granulation1 To avoid powder segregation
2 To enhance the flow of powder
3 Granules have higher porosity than powders
4 To improve the compressibility of powders
5 Avoid dustiness The granulation of toxic materials will reduce the hazard of generation of toxic dust which may arise during the handling of the powders
6 Materials which are slightly hygroscope may adhere amp form a cake if stored as a powder
7 Granules being denser than the parent powder mix occupy less volume per unit weight
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
WET GRANULATION Wet granulation is a widely employed method for the production of compressed tablets
The steps required are(a) weighing and blending the ingredients(b) preparing a dampened powder or a damp mass(c) screening the dampened powder or damp mass into pellets
or granules(d) drying the granulation(e) sizing the granulation by dry screening(f) adding lubricant and blending(g) forming tablets by compression
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Weighing and Blending Specified quantities of active ingredient diluent or filler and disintegrating agent are mixed by mechanical powder blender or mixer until uniform Fillers include1 lactose2 microcrystalline cellulose3 starch4 powdered sucrose5 calcium phosphate
The choice of filler usually is based on6 the experience of the manufacturer with the material7 its relative cost8 its compatibility with the other formulation ingredients
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
EXAMPLEFor example calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the gastrointestinal tract
Among the fillers most preferred are lactose because of its solubility and
compatibility microcrystalline cellulose because of its easy
compaction compatibility and consistent uniformity of supply
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Disintegrating agents include1 croscarmellose2 corn and potato starches3 sodium starch glycolate4 sodium carboxymethylcellulose5 polyvinylpyrroli-done (PVP)6 crospovidone7 cation exchange resins8 alginic acid9 other materials that swell or expand on exposure to
moisture and effect the rupture or breakup of the tablet in the gastrointestinal tract
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Croscarmellose (2) and sodium starch glycolate (5) are often preferred because of their high water uptake rapid action
One commercial brand of sodium starch glycolate is reported to swell up to 300 of its volume in water
When starch is employed 5 to 10 is usually suitable but up to about 20 may be used to promote more rapid tablet disintegration
The total amount of disintegrant used is not always added in preparing the granulation
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Preparing the Damp Mass
A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles
A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Among binding agents solutions of povidone an aqueous preparation of
cornstarch (10 to 20) glucose solution (25 to 50) molasses methylcellulose (3) carboxymethyl- cellulose microcrystalline cellulose
If the drug substance is adversely affected by an aqueous binder a nonaqueous solution or dry binder may be used
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The amount of binding agent used is part of the operatorrsquos art however the resulting binderndashpowder mixture should compact when squeezed in the hand
The binding agent contributes to adhesion of the granules to one another and maintains the integrity of the tablet after compression
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Overwetting can result in granules that are too hard for proper tablet formation
Underwetting can result in tablets that are too soft and tend to crumble
When desired a colorant or flavorant may be added to the binding agent to prepare a granulation with an added feature
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Screening the Damp Mass into Pellets or Granules
The dampened powder granules are screened or the wet mass is pressed through a screen (usually 6 or 8 mesh) to prepare the granules
This may be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus
The resultant granules are spread evenly on large lined trays and dried to consistent weight or constant moisture content
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Drying the Granulation
Granules may be dried in thermostatically cotrolled ovens that constantly record the time temperature and humidity
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Sizing the Granulation by Dry Screening After drying the granules are passed through a screen of a smaller mesh
than that used to prepare the original granulation
The degree to which the granules are reduced depends on the size of the punches to be used
In general the smaller the tablet to be produced the smaller the granules
Screens of 12- to 20-mesh size are generally used for this purpose
Sizing of the granules is necessary so that the die cavities for tablet compression may be completely and rapidly filled by the free-flowing granulation
Voids or air spaces left by too large a granulation result in the production of uneven tablets
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Adding Lubrication and Blending
After dry screening a dry lubricant is dusted over the spread-out granulation through a fine- mesh screen
Lubricants contribute to the preparation of compressed tablets in several ways
1 They improve the flow of the granulation in the hopper to the die cavity
2 They prevent adhesion of the tablet formulation to the punches and dies during compression
3 They reduce friction between the tablet and the die wall during the ejection of the tablet from the machine
4 They give a sheen to the finished tablet
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Among the more commonly used lubricants are magnesium stearate calcium stearate stearic acid talc sodium stearyl fumarate
Magnesium stearate is most used The quantity of lubricant used varies from one
operation to another but usually ranges from about 01 to 5 of the weight of the granulation
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
ALL-IN-ONE GRANULATION METHODS Technologic advances
now allow the entire process of granulation to be completed in a continuous fluid bed process using a single piece of equipment the fluid bed granulator
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The fluid bed granulator performs the following steps (a) preblending the formulation powder including
active ingredients fillers and disintegrants in a bed with fluidized air
(b) granulating the mixture by spraying onto the fluidized powder bed a suitable liquid binder such as an aqueous solution of acacia hydroxypropyl cellulose or povidone
(c) drying the granulated product to the desired moisture content
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Another method microwave vacuum processing also allows the powders to be
mixed wetted agglomerated dried within the confines of a single piece of equipment
o The wet mass is dried by gentle mixing vacuum and microwave
o The use of the microwave reduces the drying time considerably often by one fourth
o The total batch production time is usually in the range of 90 minutes
o After adding lubricants and screening the batch is ready for tablet formation or capsule filling
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Advantages of wet granulation
Advantages Reduced segregation of formulation components
during storage andor processing
Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent
Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Disadvantages1 Often several processing steps are required2 Solvents are required in the process this
leads to a number of concerns Drug degradation may occur in the presence
of the solvent The drug may be soluble in the granulation
fluid Heat is required to remove the solvent
Disadvantages of wet granulation
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
DRY GRANULATION
By the dry granulation method the powder mixture is compacted in large pieces and subsequently broken down or sized into granules
For this method either the active ingredient or the diluent must have cohesive properties
Dry granulation is especially applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Slugging After weighing and mixing the ingredients the powder
mixture is slugged or compressed into large flat tablets or pellets about 1 inch in diameter
The slugs are broken up by hand or by a mill and passed through a screen of desired mesh for sizing
Lubricant is added in the usual manner and tablets are prepared by compression
Aspirin which is hydrolyzed on exposure to moisture may be prepared into tablets after slugging
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Roller Compaction Instead of slugging powder compactors may be used to
increase the density of a powder by pressing it between rollers at 1 to 6 tons of pressure
The compacted material is broken up sized and lubricated and tablets are prepared by compression in the usual manner
The roller compaction method is often preferred to slugging
Binding agents used in roller compaction formulations include Methylcellulose hydroxy methylcellulose (6 to 12) which can produce good tablet hardness and friability
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Advantages of dry granulation
Advantages of dry granulation1 These methods are not generally
associated with alterations in drug morphology during processing
2 No heat or solvents are required
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Disadvantages of dry granulation1 Specialist equipment is required for granulation by roller
compaction
2 Segregation of components may occur mixing
3 There may be issues regarding powder flow
4 The final tablets produced by dry granulation tend to be softer than those produced by wet granulation
5 Slugging and roller compaction lead to the generation of considerable dust
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
DIRECT COMPRESSION TABLETING
Some granular chemicals like potassium chloride possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation
For chemicals lacking this quality special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression
These excipients include fillers such as spray-dried lactose microcrystals of alpha-monohydrate lactose sucrosendashinvert sugarndashcorn starch mixtures microcrystalline cellulose crystalline maltose dicalcium phosphate
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Disintegrating agents such as direct compression starch sodium carboxymethyl starch cross-linked carboxymethylcellulose fibers cross-linked polyvinylpyrrolidone
lubricants such as magnesium stearate talc
Glidants such as fumed silicon dioxide
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Advantages and disadvantages of direct compressionAdvantages 1 Low labour input2 A dry process3 Fewest processing steps
Disadvantages4 Stratification (layers) may occur due to differences in particle size and bulk density
which results poor content uniformity
5 A large dose drug may cause problem in direct compression It requires diluents The tablet becomes large in size which is difficult to swallow and also costly
6 During handling of dry materials static charge may form which may present uniform distribution of drug
7 Direct compression diluent may interact with the drug For example amine drug with Lactose produce discoloration of tablet
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
1 Milling and mixing of drugs and excipients
2 Preparation of binder solution
2 Compression into slugs or roll compaction
2 Compression of tablet
3 Wet massing by addition of binder solution or granulating solvent
3 Milling and screening of slugs and compacted powder
4 Screening of wet mass 4 Mixing with disintegrantlubricant
5 Drying of the wet granules
5 Compression of tablet
6 Screening of dry granules7 Blending with disintegrant lubricant and8 Compression of tablet
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Compression process
Filling By gravitational flow (or mechanical conveyors) of powder from hopper via the die table into die The die is closed at its lower end by the lower punch
Compression The upper punch descends and enters the die and the powder is compressed until a tablet is formed During the compression phase the lower punch can be stationary or can move upwards in the die After maximum applied force is reached the upper punch leaves the powder
Ejection During this phase the lower punch rises until its tip reaches the level of the top of the die The tablet is subsequently removed from the die and die table by a pushing device
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablet compression machine
1 Hopper for holding and feeding granulation to be compressed
2 Dies that define the size and shape of the tablet
3 Punches for compressing the granulation within the dies
4 Cam tracks for guiding the movement of the punches
5 Feeding mechanisms for moving granulation from the hopper into the die
6 Tablet ejector
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablets Defects
Capping
LaminationSticking amp Picking
Hardness variation
Chipping
SplittingErosion Thicknes
s variation
Black Spots
Double Impressions
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
1 Capping
CAPPING happened when the upper or lower segment of the tablet separates horizontally either partially or completely from the main body of a tablet and comes off as a cap during ejection from the tablet press or during handling or other process
Reason Capping is usually due to the1 Air ndash entrapment2 Large amount of fines in the
granulation 3 Too dry or very low moisture
content4 Insufficient amount of binder5 Poorly finished dies and or
punches
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
2 LaminationLamination is the separation of a tablet into two or
more distinct horizontal layers
Reason1 Air - entrapment during compression2 Too much of hydrophobic lubricant eg Magnesium-stearate3 Rapid decompression
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
3 Sticking amp Picking Sticking is one of the most common problems of tablet making It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet
Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling
Weight variation ---- hardness ndash thickness- dissolution moisture contentparticle size distributionBad quality of the punches ndash surface not smoothAir entrapment
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablet Dedusting To remove traces of loose powder
adhering to tablets following compression the tablets are conveyed directly from the tableting machine to a deduster
The compressed tablets may then be coated
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Tablet coating
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Coated tablets are defined as ldquotablets covered with one or more layers of mixture of various substances
Coating may also contain active ingredient
Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates
Tablet coating
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Objectives of Coatingwhy coating
1 Reduce influence of atmosphere 2 Mask taste odor amp color of drug 3 Control or Modify drug Release CR SR helliphellip4 Protect drug against GI environment Enteric coating 5 Avoid irritation of esophagus and stomach6 Incompatibility Drug amp drug 7 Improve elegance color imprinting amp patient
acceptance 8 Increases the mechanical strength of the core tablet 9 To prevent direct contact with the drug substance
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Types of coating processes
The main types are used in the pharmaceutical industry today
CoatingFunctional
coating
Non Functional coating
- Sugar coating Compression coating
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The main steps involved in the coating of tablets are as follows
The tablets (or granules) are placed within the coating apparatus and agitated
The coating solution is sprayed on to the surface of the tablets
Warm air is passed over the tablets to facilitate removal of the solvent from the adsorbed layer of coating solution on the surface of the tablets
When the solvent has evaporated the tablets will be coated with the solid component of the original coating solution
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Sugar coatingbull Description of tablets Smooth rounded and polished to a high glossbull Process Multistage process involving 6 separate operations
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Sugar coating Sealing tablet core application of a water impermeable
polymer such as Shellac cellulose acetate phthalate and polyvinyl acetate phthalate which protects the core from moisture increasing its shelf life
Sub coating After the tablets are waterproofed if needed three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tab- let and provides rounding The sucrose and water syrup also contains gelatin acacia or PVP to enhance coating
Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup This syrup is sucrose based with or without additional com- ponents such as starch and calcium carbonate
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Sugar coating Colouring - for aesthetic purposes often titanium
based pigments are included
Polishing - effectively polished to give characteristic shine commonly using beeswax carnauba wax
Printing -permanent ink for characterization
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Film coating Coating tablets capsules or pellets by surrounding them
with a thin layer of polymeric material Process Single stage process which involves spraying a
coatingThe solution or suspension is sprayed to a rotating tablet bed followed by drying which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Film coating
Film coating contains the following1 Film forming Polymer
2 Solvent3 Plasticizer4 Colourant
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Film forming Polymer
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Plasticizer
LOW MOLECULAR WEIGHT ORGANIC MOLECULES CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER
- Better mechanical propertiesndash Resistance to deformation
ndash Flexible elastic films (high modulus of elasticity)
ndash Continuous film
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Solvent
Solvent
organic
Environmental Safety
Financial Solvent residues
P WaterProduct ndash Stability
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Film-coating solutions may be nonaqueous or aqueous
The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets
1 A film former capable of producing smooth thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes Example cellulose acetate phthalate
2 An alloying substance providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug Example polyethylene glycol
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
3 A plasticizer to produce flexibility and elasticity of the coating and thus provide durability Example castor oil
4 A surfactant to enhance spreadability of the film during application Example polyoxyethylene sorbitan derivatives
5 Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive Examples Opaquant titanium dioxide colorant FDampC or DampC dyes
6 Sweeteners flavors and aromas to enhance the acceptability of the tablet by the patient Examples sweeteners saccharin flavors and aromas vanillin
7 A glossant to provide luster to the tablets without a separate polishing operation Example beeswax
8 A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example alcohol mixed with acetone
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30 ethyl cellulose pseudolatex
Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity
The low viscosity allows less water to be used in the coating dispersion requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation
In addition the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets
A plasticizer may be added to assist in the production of a dense relatively impermeable film with high gloss and mechanical strength
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
A typical aqueous film-coating formulation contains the following
1 Film-forming polymer (7 to 18) Examples cellulose ether polymers such as hydroxypropyl methylcellulose hydroxypropyl cellulose and methylcellulose
2 Plasticizer (05 to 20) Examples glycerin propylene glycol polyethylene glycol diethyl phthalate and dibutyl subacetate
3 Colorant and opacifier (25 to 8) Examples FDampC or DampC lakes and iron oxide pigments
4 Vehicle (water to make 100)
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Film coating Sugar coating
Film coatingbullTablet appearance Retains shape of original coreSmall weight increase of 2-10 due to coating material logo or lsquobreak linesrsquo possibleNo Wait amp size variation
bullTablet appearanceRounded with high degree of polishLarger weight increase 30-100 due to coating material Logo or lsquobreak linesrsquo are ImpossibleWait amp size variation within the batch or from batch to batch
Sugar coating
bullProcess Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings
bullProcessDifficult to automated Considerable training operation Multi stage process More time Not able to be used for controlled Release
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Problems of Film Coating
PICKING STICKING small holes pulled in film or small amount of the film flaking from the tablet surface
PEELING the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Twinning two or more tablets that stick together Common problem with flat or capsule shaped tablets
Roughness or orange peel film not smooth
Problems of Film Coating
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Problems of Film Coating
CRACKING Torn or cracked films
CORE EROSION loss of material from tablet surface
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Problems of Film CoatingColor Variation or mottling
LOGO BRIDGING the coating fills in the logo on the tablets
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Functional coatingsFunctional coatings are coatings which perform a pharmaceutical
function Enteric coating Controlled release coating
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive polymer which swell or solubilize in response to an increase in pH to release the drug
Aims of Enteric protection 1 Protection of active ingredients from the acidic environment of the stomach
2 Protection from local irritation of the stomach mucosa
3 Release of active ingredient in specific target area within gastrointestinal tract
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Among the materials used in enteric coatings are
1 Pharmaceutical shellac2 Hydroxypropyl methylcellulose
phthalate3 Polyvinyl acetate phthalate4 Diethyl phthalate5 Cellulose acetate phthalate
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
FLUID BED COATER
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Press coating
Press coating process involves compaction of coating material around a preformed core
for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment Compression coating is a dry process
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
COMPRESSION COATING
Compared to sugarcoating using pans compression coating is more uniform and uses less coating material resulting in tablets that are lighter smaller and easier to swallow and less expensive to package and ship
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
CHANGES ON SOLID DOSAGE FORM
Starting materials Manufacturing process
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
PACKAGING AND STORING TABLETSTablets are stored in tight containers in places of low humidity and protected from extremes in temperature
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Products that are prone to decomposition by moisture generally are packaged with a desiccant packet
Drugs that are adversely affected by light are packaged in light-resistant containers
With a few exceptions tablets that are properly stored will remain stable for several years or more
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Upon aging Hardness - The increase in tablet
hardness can frequently be attributed to the increased adhesion of the binding agent and other formulative components within the tablet
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
In tablets containing volatile drugs such as nitroglycerin the drug may migrate between tablets in the container resulting in a lack of uniformity among the tablets
Also packing materials such as cotton and rayon in contact with nitroglycerin tablets may absorb varying amounts of nitroglycerin reducing potency of the tablets
The USP directs that nitroglycerin tablets be preserved in tight containers preferably of glass at
controlled room temperature
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Also migration within tablets can occur resulting in unequal distribution within a single tablet this can be problematic if the tablet is scored and designed to be broken in half where the two halves may not contain equal portions of the drug
Storage of a container next to a heat source may result in greater loss or movement of the volatile drug in the
portion of the bottle closest to the heat
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The USP further directs that nitroglycerin tablets be dispensed in the original unopened container labeled with the following statement directed to the patient ldquoWarning to prevent loss of potency keep these tablets in the original container or in a supplemental nitroglycerin container specifically labeled as being suitable for nitroglycerin tablets Close tightly immediately after userdquo (4)
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
LOZENGES LOLLIPOPS
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Chewable tablets Chewable tablets are pleasant-tasting tablets
formulated to disintegrate smoothly in the mouth with or without chewing
They are prepared by wet granulation and compression using only minimal degrees of pressure to produce a soft tablet
Generally chewable tablets do not contain disintegrants so patients must be counseled to chew the tablets thoroughly and not swallow them whole
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Mannitol a white crystalline hexahydric alcohol is used as the excipient in most chewable tablets
Mannitol is about 70 as sweet as sucrose with a cool feel in the mouth
Mannitol accounts for 50 or more of the weight of many chewable tablet formulations
Sometimes other sweetening agents such as sorbitol lactose dextrose crystalline maltose glucose may be substituted for part or all of the mannitol Xylitol may be used in the preparation of sugar- free chewable tablets
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
Among the types of products prepared as chewable tablets are1 antacids (eg calcium carbonate)2 antibiotics (eg erythromycin)3 anti-infective agents (eg didanosine)4 anticonvulsants (eg carbamazepine)5 vasodilators (eg isosorbide dinitrate)6 analgesics (eg acetaminophen)7 various vitamins8 Coldndash allergy combination tablets
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-
The following is a formula for a typical chewable antacid tablet
Aluminum hydroxide 3250mg
Mannitol 8120mg
Sodium saccharin 04mg
Sorbitol (10 wv solution) 325mg
Magnesium stearate 250mg
Mint flavor concentrate 40mg
- Tablets
- Definition
- Slide 3
- Advantages of tablets
- Disadvantages of tablets
- Tableting machine
- Slide 7
- TYPES OF TABLETS
- Slide 9
- Slide 10
- Slide 11
- MULTIPLY COMPRESSED TABLETS
- Slide 13
- SUGARCOATED TABLETS
- FILM-COATED TABLETS
- GELATIN-COATED TABLETS
- ENTERIC-COATED TABLETS
- BUCCAL AND SUBLINGUAL TABLETS
- Slide 19
- CHEWABLE TABLETS
- EFFERVESCENT TABLETS
- MOLDED TABLETS
- TABLET TRITURATES
- Slide 24
- HYPODERMIC TABLETS
- Slide 26
- DISPENSING TABLETS
- IMMEDIATE-RELEASE TABLETS
- EXTENDED-RELEASE TABLETS
- Slide 30
- VAGINAL TABLETS
- INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
- Slide 33
- Slide 34
- Slide 35
- COMPRESSED TABLETS
- Slide 37
- Slide 38
- QUALITY STANDARDS AND COMPENDIAL REQUIREMENTS
- 1 Tablet Weight and USP Weight Variation Test
- Slide 41
- Content Uniformity
- 3 Tablet Thickness
- Slide 44
- 4 Tablet Hardness and Friability
- Slide 46
- Slide 47
- 5 Tablet Disintegration
- Slide 49
- Slide 50
- Slide 51
- 6 Tablet Dissolution
- Slide 53
- Slide 54
- Slide 55
- COMPRESSED TABLET MANUFACTURE
- Slide 57
- Reasons for Granulation
- Slide 59
- Weighing and Blending
- EXAMPLE
- Slide 62
- Slide 63
- Preparing the Damp Mass
- Slide 65
- Slide 66
- Slide 67
- Screening the Damp Mass into Pellets or Granules
- Drying the Granulation
- Sizing the Granulation by Dry Screening
- Adding Lubrication and Blending
- Slide 72
- Slide 73
- ALL-IN-ONE GRANULATION METHODS
- Slide 75
- Slide 76
- Slide 77
- Slide 78
- Advantages of wet granulation
- Disadvantages of wet granulation
- DRY GRANULATION
- Slugging
- Roller Compaction
- Advantages of dry granulation
- Slide 85
- Slide 86
- Slide 87
- DIRECT COMPRESSION TABLETING
- Slide 89
- Advantages and disadvantages of direct compression
- Slide 91
- Slide 92
- Compression process
- Slide 94
- Slide 95
- Tablet compression machine
- Slide 97
- Tablets Defects
- 1 Capping
- 2 Lamination
- Slide 101
- 3 Sticking amp Picking
- Slide 103
- Tablet Dedusting
- Tablet coating
- Tablet coating (2)
- Slide 107
- Types of coating processes
- The main steps involved in the coating of tablets are as follow
- Slide 110
- Slide 111
- Sugar coating
- Sugar coating (2)
- Sugar coating (3)
- Film coating
- Film coating (2)
- Slide 117
- Plasticizer
- Solvent
- Slide 120
- Slide 121
- Slide 122
- Slide 123
- Film coating Sugar coating
- Problems of Film Coating
- Problems of Film Coating (2)
- Problems of Film Coating (3)
- Problems of Film Coating (4)
- Functional coatings
- ENTERIC COATING
- Slide 131
- FLUID BED COATER
- Slide 133
- Press coating
- COMPRESSION COATING
- CHANGES ON SOLID DOSAGE FORM
- PACKAGING AND STORING TABLETS
- Slide 138
- Upon aging
- Slide 140
- Slide 141
- Slide 142
- OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION
- Chewable tablets
- Slide 145
- Slide 146
- The following is a formula for a typical chewable antacid table
-