tablets - glocal university
TRANSCRIPT
TABLETS
Aseel Samaro
Definition
Definition according to the BP
Tablets 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 tablets
1. 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 tablets
1. Some drugs resist compression into densecompact
1. Drugs with poor wetting, slow dissolution,intermediate to large dosages may be difficultor impossible to formulate & manufacture astablet that provide adequate or fill drugbioavailability
1. Bitter taste drugs, drugs with an objectionableodor, or sensitive to oxygen or moisture mayrequire
Encapsulation or entrapment prior tocompression or
The tablets require coating
Tableting machine
TYPES OF TABLETS
1. COMPRESSED TABLETS
In addition to the medicinal agent or agents,compressed tablets usually contain a number ofpharmaceutical adjuncts, including the following:
Diluents or fillers: which add the necessary bulkto a formulation to prepare tablets of the desiredsize.
Binders or adhesives: which promote adhesionof the particles of the formulation, allowing agranulation to be prepared and maintaining theintegrity 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
Mult ip ly compressedtablets are prepared bys u b j e c t i n g t h e f i l lmaterial to more than as ing le compress ion .
The result may be amultiple-layer tablet or atablet within a tablet, theinner tablet being thec o re and the ou te rportion 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 incompatibility
2. staged drug release
3. 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 oran uncolored sugar layer.
The coating is water soluble and quickly dissolvesafter swallowing.
1. The sugarcoat protects the enclosed drug fromthe environment and provides a barrier toobjectionable taste or odor.
2. The sugarcoat also enhances the appearance ofthe compressed tablet and permits imprintingof identifying manufacturer’s information.
Among the disadvantages to sugarcoating tablets arethe time and expertise required in the coatingprocess and the increase in size, weight, andshipping costs.
Sugarcoating may add 50% to the weight and bulk ofthe uncoated tablet.
FILM-COATED TABLETS
Film-coated tablets are compressed tablets coatedwith a thin layer of a polymer capable of forming askin-like film.
The film is usually colored and has the advantage over sugarcoatings in that it is:
1. more durable
2. less bulky
3. less time- consuming to apply.
By its composition, the coating is designed to ruptureand expose the core tablet at the desired location inthe 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 unchangedthrough the stomach to the intestines,where the tablets disintegrate and allowdrug dissolution and absorption and/oreffect.
Enteric coatings are employed whenthe drug substance:
is destroyed by gastric acid or
is particularly irritating to the gastricmucosa or
when bypass of the stomachsubstantially enhances drugabsorption.
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 aredestroyed by the gastric juice and/or arepoorly absorbed from the gastrointestinal tract.
Buccal tablets are designed to erode slowly,whereas those for sublingual use (such asnitroglycerin) dissolve promptly and providerapid drug effects.
Lozenges or troches are disc-shaped soliddosage forms containing a medicinal agentand generally a flavoring substance in a hardcandy or sugar base.
They are intended to be slowly dissolved inthe oral cavity, usually for local effects,although some are formulated for systemicabsorption.
CHEWABLE TABLETS
Chewable tablets, which havea smooth, rapid disintegrationwhen chewed or allowed todissolve in the mouth, have acreamy base, usually ofspecially flavored and coloredmannitol.
Chewable tablets areespecially useful foradministration of large tabletsto children and adults whohave difficulty swallowing soliddosage forms.
EFFERVESCENT TABLETS
Effervescent tablets areprepared by compressinggranular effervescent salts thatrelease gas when in contact withwater.
These tablets generally containmedicinal substances thatdissolve rapidly when added towater.
The “bubble action” can assist inbreaking up the tablets andenhancing the dissolution of theactive 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 tabletscontaining small amounts of usually potent drugs.
Today, only a few tablet triturate products are available commercially, withmost of these produced by tablet compression.
Since tablet triturates must be readily and completely soluble in water, onlya 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 asnitroglycerin tablets.
Pharmacists also employ tablet triturates in compounding. For example,triturates are inserted into capsules or dissolved in liquid to provideaccurate amounts of potent drug substances.
HYPODERMIC TABLETS
Hypodermic tablets are no longer available in the United States.
They were originally used by physicians in extemporaneouspreparation 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 carriedin the physician’s medicine bag and injections prepared to meet theneeds of the individual patients.
However, the difficulty in achieving sterility and the availability ofprefabricated 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, areuncoated, bullet-shaped or ovoid tablets inserted intothe vagina for local effects.
They contain :
antibacterials for the treatment of nonspecific vaginitiscaused by Haemophilus vaginalis
antifungals for the treatment of vulvovaginitiscandidiasis caused by Candida albicans and relatedspecies.
INSTANTLY DISINTEGRATING
OR DISSOLVING TABLETS
Instant-release tablets (rapidly dissolving tablets, or RDTs) arecharacterized by disintegrating or dissolving in the mouth within 1minute, some within 10 seconds
Tablets of this type are designed for children and the elderly or forany 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 excipientsdesigned to wick water into the tablet for rapid disintegration ordissolution. They have the stability characteristics of other soliddosage forms.
The original fast-dissolving tablets were molded tablets forsublingual use.
They generally consisted of active drug and lactosemoistened with an alcohol–water mixture to form a paste.
The tablets were then molded, dried, and packaged.
For use, they were simply placed under the tongue to providea rapid onset of action for drugs such as nitroglycerin.
Also, they have been used for drugs that are destroyed in thegastrointestinal tract, such as testosterone, administeredsublingually 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 wellknown:
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 and/or codenumber
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 tablets
Punches 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 otherphysical 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-processcontrols) and verified after the production of each batch to ensure thatestablished 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 theweight of the tablet.
The volume of fill is adjusted with the first few tablets to yield thedesired weight and content.
For example, if a tablet is to contain 20 mg of a drug substanceand if 100,000 tablets are to be produced, 2,000 g of drug isincluded in the formula.
After the addition of the pharmaceutical additives, such as thediluent, disintegrant, lubricant, and binder, the formulation mayweigh 20 kg, which means that each tablet must weigh 200 mgfor 20 mg of drug to be present
Thus, the depth of fill in the tablet die must be adjusted to hold avolume of granulation weighing 200mg.
During production, sample tablets are periodically removed forvisual 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 averageweight is calculated.
The tablets are assayed and the content of active ingredient in eachof the 10 tablets is calculated assuming homogeneous drugdistribution.
2. Content Uniformity
By the USP method, 10 dosage units are individuallyassayed for their content according to the methoddescribed in the individual monograph.
Unless otherwise stated in the monograph, therequirements for content uniformity are met if theamount of active ingredient in each dosage unit lieswithin the range of 85% to 115% of the label claim andthe 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 by:
1. The diameter of the die
2. The amount of fill permitted to enter the die
3. The compaction characteristics of the fill material
4. The force or pressure applied during compression.
To produce tablets of uniform thickness during and between batchproductions for the same formulation, care must be exercised toemploy the same factors of fill, die, and pressure.
The degree of pressure affects not only thickness but also hardness ofthe tablet; hardness is perhaps the more important criterion since it canaffect disintegration and dissolution.
4. Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3,000 andas much as 40,000lb of force
In production of tablets. Generally, the greater the pressureapplied, the harder the tablets, although the characteristics of thegranulation also have a bearing on hardness.
Certain tablets, such as lozenges and buccal tablets, that areintended to dissolve slowly are intentionally made hard; othertablets, 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 areused to measure the degree of force (in kilograms, pounds, or inarbitrary units) required to break a tablet.
A force of about 4kg is considered the minimum requirement for asatisfactory tablet.
A tablet’s durability: may be determined through the use of afriabilator.
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 fluidsfor dissolution.
Tablet disintegration also is important for tablets containing medicinalagents (such as antacids and antidiarrheals) that are not intended to beabsorbed but rather to act locally within the gastrointestinal tract.
In these instances, tablet disintegration provides drug particles with anincreased surface area for activity within the gastrointestinal tract.
All USP tablets must pass a test for disintegration, which is conducted invitro 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 upona 10-mesh stainless steel wire screen.
Tablets must disintegrate within the times set in the individualmonograph, usually 30 minutes, but varying from about 2minutes for nitroglycerin tablets to up to 4 hours for buccaltablets.
If one or more tablets fail to disintegrate, additional testsprescribed by the USP must be performed.
Enteric-coated tablets are similarly tested, except that thetablets are tested in simulated gastric fluid for 1 hour, afterwhich no sign of disintegration, cracking, or softening must beseen.
They are then actively immersed in the simulated intestinalfluid for the time stated in the individual monograph, duringwhich time the tablets disintegrate completely for a positivetest.
6. Tablet Dissolution
In vitro dissolution testing of solid dosage forms isimportant for a number of reasons :
It guides formulation and product development towardproduct optimization.
Dissolution studies in the early stages of a product’sdevelopment allow differentiation betweenformulations and correlations identified with in vivobioavailability data.
Consistent in vitro dissolution testing ensuresbioequivalence 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 product’s in vivo bioavailability.
The system relates combinations of a drug’s solubility (high or low) and its intestinal
permeability (high or low) as a possible basis for predicting the likelihood of
achieving a successful in vivo–in 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 -
1. 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.
1. 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 thedrug in a tablet.
A number of formulation and manufacturing factors can affect thedisintegration and dissolution of a tablet, including
1. particle size of the drug substance
2. solubility and hygroscopicity of the formulation
3. type and concentration of the disintegrant
4. binder
5. lubricant
6. manufacturing method
7. particularly the compactness of the granulation
8. compression force used in tableting
9. any in-process variables
COMPRESSED TABLET
MANUFACTURE
Compressed tablets may be made by three basicmethods:
wet granulation
dry granulation
direct compression
Most powdered medicinal agents require addition ofexcipients such as:
diluents
binders
disintegrants
Lubricants
to provide the desired characteristics for tablet manufactureand 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 Granulation
1. 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 oftoxic dust, which may arise during the handling of the powders.
6. Materials, which are slightly hygroscope, may adhere & 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 include:
1. lactose
2. microcrystalline cellulose
3. starch
4. powdered sucrose
5. calcium phosphate.
The choice of filler usually is based on:
1. the experience of the manufacturer with the material
2. its relative cost
3. its compatibility with the other formulation ingredients.
EXAMPLE
For 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 include:
1. croscarmellose
2. corn and potato starches
3. sodium starch glycolate
4. sodium carboxymethylcellulose
5. polyvinylpyrroli-done (PVP)
6. crospovidone
7. cation exchange resins
8. alginic acid
9. 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 ofcornstarch (10% to 20%)
glucose solution (25% to 50%)
molasses
methylcellulose (3%)
carboxymethyl- cellulose
microcrystalline cellulose.
If the drug substance is adversely affected by anaqueous binder, a nonaqueous solution, or dry binder,may be used.
The amount of binding agent used is part of the
operator’s art; however, the resulting binder–
powder 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 orthe wet mass is pressed through a screen (usually6 or 8 mesh) to prepare the granules.
This may be done by hand or with specialequipment that prepares the granules by extrusionthrough perforations in the apparatus.
The resultant granules are spread evenly on largelined trays and dried to consistent weight orconstant 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 meshthan that used to prepare the original granulation.
The degree to which the granules are reduced depends on the size of thepunches 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 tabletcompression may be completely and rapidly filled by the free-flowinggranulation.
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 ofcompressed tablets in several ways:
1. They improve the flow of the granulation in thehopper to the die cavity.
2. They prevent adhesion of the tablet formulation tothe punches and dies during compression.
3. They reduce friction between the tablet and the diewall during the ejection of the tablet from themachine.
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 oneoperation to another but usually ranges from about0.1% 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 powdersto 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 byone 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 tabletformation or capsule filling.
Advantages of wet
granulationAdvantages
Reduced segregation of formulation componentsduring storage and/or processing
Useful technique for the manufacture of tabletscontaining low and or high concentrations oftherapeutic agent
Employs conventional excipients and therefore isnot dependent on the inclusion of special gradesof excipients
Disadvantages
1. Often several processing steps are required
2. 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 powdermixture is compacted in large pieces andsubsequently 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 tomaterials that cannot be prepared by wetgranulation because they degrade in moisture orthe elevated temperatures required for drying thegranules.
Slugging
After weighing and mixing the ingredients, the powdermixture is slugged, or compressed, into large flattablets or pellets about 1 inch in diameter.
The slugs are broken up by hand or by a mill andpassed through a screen of desired mesh for sizing.
Lubricant is added in the usual manner, and tabletsare 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 granulation
1. These methods are not generally
associated with alterations in drug
morphology during processing.
2. No heat or solvents are required.
Disadvantages of dry granulation
1. Specialist equipment is required for granulation by rollercompaction.
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 besofter than those produced by wet granulation
5. Slugging and roller compaction lead to the generation ofconsiderable 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
sucrose–invert sugar–corn 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 compression
Advantages:1. Low labour input2. A dry process3. Fewest processing steps
Disadvantages:1. Stratification (layers) may occur due to differences in particle size and
bulk density which results poor content uniformity.
2. A large dose drug may cause problem in direct compression. It requiresdiluents. The tablet becomes large in size which is difficult to swallowand also costly.
3. During handling of dry materials static charge may form which maypresent uniform distribution of drug.
4. 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
disintegrant/lubricant
5. Drying of the wet granules 5. Compression of tablet
6. Screening of dry granules
7. Blending with disintegrant /
lubricant and
8. Compression of tablet
Compression process
Filling: By gravitational flow (or mechanical conveyors) of powder fromhopper via the die table into die. The die is closed at its lower end by thelower punch.
Compression: The upper punch descends and enters the die and the powderis compressed until a tablet is formed. During the compression phase, thelower punch can be stationary or can move upwards in the die. Aftermaximum applied force is reached, the upper punch leaves the powder
Ejection: During this phase, the lower punch rises until its tip reaches thelevel of the top of the die. The tablet is subsequently removed from thedie 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 intothe die
6. Tablet ejector
Tablets Defects
Cappin
g
Lamination
Sticking &
Picking
Hardness
variation
Chippin
g
Splitting
Erosio
n
Thickness
variation
Black
Spots
Double Impressions
1. Capping
CAPPING happened when the upper orlower segment of the tablet separateshorizontally, either partially or completelyfrom the main body of a tablet and comes offas a cap, during ejection from the tabletpress, or during handling or other process.
Reason: Capping is usually due to the
1. Air – entrapment
2. Large amount of fines in the
granulation
3. Too dry or very low moisture content
4. Insufficient amount of binder
5. Poorly finished dies and or punches
2. Lamination
Lamination is the separation of a tablet into two or more distinct horizontal layers.
Reason:
1. Air - entrapment during compression
2. Too much of hydrophobic lubricant e.g.: Magnesium-stearate
3. Rapid decompression
3. Sticking & 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 – thickness-
dissolution
moisture content
particle size distribution
Bad quality of the punches – surface not
smooth
Air 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 “tablets covered with oneor more layers of mixture of various substances.
Coating may also contain active ingredient.
Substances used for coating are usually applied assolution or suspension under conditions where vehicleevaporates.
Tablet coating
Objectives of Coating/why coating
1. Reduce influence of atmosphere 2. Mask: taste odor & color of drug 3. Control or Modify drug Release: CR, SR …….4. Protect drug against GI environment : Enteric coating 5. Avoid irritation of esophagus and stomach6. Incompatibility: Drug & drug 7. Improve elegance : color imprinting & 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
Coating
Functional 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 coatingapparatus 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 thesolvent from the adsorbed layer of coating solution on thesurface of the tablets.
When the solvent has evaporated, the tablets will be coatedwith the solid component of the original coating solution.
Sugar coating
• Description of tablets: Smooth, rounded and polished to a high
gloss.
• 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 titaniumbased pigments are included.
Polishing - effectively polished to give characteristicshine, 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 coating
The solution or suspension is sprayed to a rotatingtablet bed followed by drying, which facilitates theremoval of the solvent leaving behind thedeposition of thin film of coating materials aroundeach tablet
Film coating
Film coating contains the following;1. 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 properties
– Resistance to deformation
– Flexible, elastic films (high modulus of elasticity)
– Continuous film
Solvent
Solvent
organic
Environmental Safety Financial
Solvent residues
P. WaterProduct – Stability
Film-coating solutions may be nonaqueous or aqueous.
The nonaqueous solutions contain the following types ofmaterials to provide the desired coating to the tablets:
1. A film former capable of producing smooth, thin filmsreproducible under conventional coating conditions andapplicable to a variety of tablet shapes. Example: celluloseacetate phthalate.
2. An alloying substance providing water solubility orpermeability to the film to ensure penetration by body fluidsand therapeutic availability of the drug. Example:polyethylene glycol.
3. A plasticizer to produce flexibility and elasticity of the coating and thus providedurability. 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 tabletshandsome and distinctive. Examples: Opaquant, titanium dioxide; colorant, FD&Cor D&C dyes.
6. Sweeteners, flavors, and aromas to enhance the acceptability of the tablet bythe 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 tabletswhile allowing rapid evaporation to permit an effective yet speedy operation.Example: alcohol mixed with acetone.
One commercial water-based colloidal coating dispersion calledAquacoat (FMC Corporation) contains a 30% ethyl cellulosepseudolatex.
Pseudolatex dispersions have a high solids content for greatercoating ability and a relatively low viscosity.
The low viscosity allows less water to be used in the coatingdispersion, requiring less evaporation and reducing the likelihoodthat water will interfere with tablet formulation.
In addition, the low viscosity permits greater coat penetration intothe 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 mechanicalstrength.
A typical aqueous film-coating formulation contains the following:
1. Film-forming polymer (7% to 18%). Examples: celluloseether polymers such as hydroxypropyl methylcellulose,hydroxypropyl cellulose, and methylcellulose.
2. Plasticizer (0.5% to 2.0%). Examples: glycerin, propyleneglycol, polyethylene glycol, diethyl phthalate, and dibutylsubacetate.
3. Colorant and opacifier (2.5% to 8%). Examples: FD&C orD&C lakes and iron oxide pigments.
4. Vehicle (water, to make 100%).
Film coating Sugar
coating
Film coating
•Tablet appearance Retains shape of original coreSmall weight increase of 2-10 % due to coating material logo or ‘break lines’ possibleNo Wait & size variation
•Tablet appearanceRounded with high degree of polishLarger weight increase 30-100 %due to coating material Logo or ‘break lines’ are ImpossibleWait & size variation within the batch or from batch to batch
Sugar coating
•Process Can be automated Easy training operationSingle stage process Less Time Easily adaptable for controlledrelease allows for functionalcoatings.
•ProcessDifficult to automated Considerable training operationMulti stage processMore time Not able to be used for controlled Release
Problems of Film Coating
PICKING/ STICKING: small holes pulledin film or small amount of the filmflaking from the tablet surface
PEELING: the coating peels away fromthe tablet surface or large amount ofthe 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 Coating
Color Variation or mottling
LOGO BRIDGING: the coating fills in the logo on the tablets
Functional coatings
Functional 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 fromdisintegration in the acidic environment of the stomach by employing pHsensitive polymer, which swell or solubilize in response to an increase in pH torelease 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 shellac
2. Hydroxypropyl methylcellulose phthalate
3. Polyvinyl acetate phthalate
4. Diethyl phthalate
5. 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
TABLETS
Tablets are stored in tight containers, in places of low
humidity, and protected from extremes in temperature.
Products that are prone todecomposition by moisturegenerally are packaged with adesiccant packet.
Drugs that are adversely affectedby light are packaged in light-resistant containers.
With a few exceptions, tablets thatare properly stored will remainstable 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 asnitroglycerin, the drug may migrate between tabletsin the container, resulting in a lack of uniformityamong the tablets.
Also, packing materials, such as cotton and rayon, incontact with nitroglycerin tablets may absorb varyingamounts of nitroglycerin, reducing potency of thetablets.
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. “Warning: 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 use” (4).
OTHER SOLID DOSAGE FORMS FOR
ORAL ADMINISTRATION
LOZENGES
LOLLIPOPS
Chewable tablets
Chewable tablets are pleasant-tasting tabletsformulated to disintegrate smoothly in the mouthwith or without chewing.
They are prepared by wet granulation andcompression, using only minimal degrees ofpressure to produce a soft tablet.
Generally, chewable tablets do not containdisintegrants, so patients must be counseled tochew the tablets thoroughly and not swallow themwhole.
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 chewabletablets are:
1. antacids (e.g., calcium carbonate)
2. antibiotics (e.g., erythromycin)
3. anti-infective agents (e.g., didanosine)
4. anticonvulsants (e.g., carbamazepine)
5. vasodilators (e.g., isosorbide dinitrate)
6. analgesics (e.g., acetaminophen)
7. various vitamins
8. Cold– allergy combination tablets.
The following is a formula for a
typical chewable antacid tablet
Aluminum hydroxide 325.0mg
Mannitol 812.0mg
Sodium saccharin 0.4mg
Sorbitol (10% w/v solution) 32.5mg
Magnesium stearate 25.0mg
Mint flavor concentrate 4.0mg