pm3125: lectures 18 to 21

Prof. R. Shanthini 22 Oct 2012

Content of Lecture 18:

- Compression & Compaction in Tablets Formation

PM3125: Lectures 18 to 21


Principle of tablet production

Active substance synthesis

Blending and Granulation

Compression

Coating

Package


Advantages and disadvantages of compressed Advantages and disadvantages of compressed tabletstablets

Types of tabletsTypes of tablets Tablet compression machineTablet compression machine Tableting methodsTableting methods

Compressed tablets

Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University


Production aspectProduction aspect Large scale production at lowest costLarge scale production at lowest cost Easiest and cheapest to package and shipEasiest and cheapest to package and ship High stabilityHigh stability

User aspect (doctor, pharmacist, patient)User aspect (doctor, pharmacist, patient) Easy to handlingEasy to handling Lightest and most compactLightest and most compact Greatest dose precision & least content variabilityGreatest dose precision & least content variability Coating can mark unpleasant tastes & improve Coating can mark unpleasant tastes & improve

acceptabilityacceptability

Advantages



Some drugs resist compression into dense Some drugs resist compression into dense compactscompacts

Drugs with poor wetting, slow dissolution, Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or intermediate to large dosages may be difficult or impossible to formulate and manufacture as a impossible to formulate and manufacture as a tablet that provide adequate or full drug tablet that provide adequate or full drug bioavailabilitybioavailability

Bitter taste drugs, drugs with an objectionable Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to require encapsulation or entrapment prior to compression or the tablets may require coating compression or the tablets may require coating

Disadvantages



Types of tablets – Production process


Compressed tabletsCompressed tablets Multiple compressed tabletsMultiple compressed tablets

Tablet within a tablets: core and shellTablet within a tablets: core and shell Multilayer tabletMultilayer tablet

Sugar coated tabletsSugar coated tablets Protect tablets from moistureProtect tablets from moisture Mask odor and flavorMask odor and flavor EleganceElegance


Types of tablets – Production process


Film coated tabletsFilm coated tablets Thin film coatThin film coat Soluble or insoluble polymer filmSoluble or insoluble polymer film

Chewable tabletsChewable tablets Rapid disintegrateRapid disintegrate Antacid, flatulance: rapid actionAntacid, flatulance: rapid action Children drugChildren drug

Effervescent tabletsEffervescent tablets Dissolve in the water before drinkDissolve in the water before drink


DrugsDrugs Fillers, diluent, bulking agentFillers, diluent, bulking agent

To make a reasonably sized tabletTo make a reasonably sized tablet BindersBinders

To bind powders together in the wet granulation To bind powders together in the wet granulation processprocess

To bind granule together during compressionTo bind granule together during compression DisintegrantsDisintegrants

To promote breakup of the tabletsTo promote breakup of the tablets To promote rapid release of the drugTo promote rapid release of the drug

Ingredients used in tablet formulations



Lubricants Lubricants To reduce the friction during tablet ejection between To reduce the friction during tablet ejection between

the walls of the tablet and the walls of the die cavitythe walls of the tablet and the walls of the die cavity GlidantsGlidants

Reducing friction between the particlesReducing friction between the particles To improve the flow properties of the granulations To improve the flow properties of the granulations

AntiadherantsAntiadherants To prevent adherence of the granules to the punch To prevent adherence of the granules to the punch

faces and diesfaces and dies

Ingredients used in tablet formulations (contd.)




Dissolution (enhancers and retardants)Dissolution (enhancers and retardants) Wetting agentsWetting agents Antioxidants Antioxidants PreservativesPreservatives Coloring agentsColoring agents Flavoring agentsFlavoring agents

Ingredients used in tablet formulations (contd.)


Essential properties of tablets


Accurate dosage of medicament, uniform in Accurate dosage of medicament, uniform in weight, appearance and diameterweight, appearance and diameter

Have the strength to withstand the rigors of Have the strength to withstand the rigors of mechanical shocks encountered in its mechanical shocks encountered in its production, packaging, shipping and dispensingproduction, packaging, shipping and dispensing

Release the medicinal agents in the body in a Release the medicinal agents in the body in a predictable and reproducible mannerpredictable and reproducible manner

Elegant product, acceptable size and shapeElegant product, acceptable size and shape Chemical and physical stabilitiesChemical and physical stabilities


Tablet production


Powders intended for Powders intended for compressioncompression into tablets into tablets must possess two essential propertiesmust possess two essential propertiesPowder fluidityPowder fluidity

The material can be transported through the The material can be transported through the hopper into the diehopper into the die

To produce tablets of a consistent weightTo produce tablets of a consistent weight Powder flow can be improved mechanically by the Powder flow can be improved mechanically by the

use of vibrators, incorporate the glidantuse of vibrators, incorporate the glidantPowder Powder compressibilitycompressibility

The property of forming a stable, intact compact The property of forming a stable, intact compact mass when pressure is appliedmass when pressure is applied


Tableting procedure


Filling Filling Compression Compression EjectionEjection


Schematic diagram showing the manufacture of single and bilayer tablets utilising uniaxial compaction.

A — Die filling

B — Compression

C — Decompression

D — Lower punch removal and reapplication of load to the upper punch

E — Tablet fully ejected

1 refers to the final compaction conditions


WET GRANULATION DRY GRANULATION DIRECT COMPRESSION

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 lubricant and disintegrant

5. Drying of the wet granules 5. Compression of tablet

6. Screening of dry granules

7. Blending with lubricant and disintegrant to produce “running powder”

8. Compression of tablet


It is a process in which primary powder particles It is a process in which primary powder particles are made to adhere to form larger, multiparticle are made to adhere to form larger, multiparticle entities called granules. entities called granules.

It is the process of collecting particles together It is the process of collecting particles together by creating bonds between them. by creating bonds between them.

Bonds are formed by compression or by using a Bonds are formed by compression or by using a binding agent. binding agent.

Granulation


Granulation (contd.)

The most common reasons given to justify The most common reasons given to justify granulating are:granulating are: To impart good flow properties to the material,To impart good flow properties to the material, To increase the apparent density of the powders,To increase the apparent density of the powders, To change the particle size distribution,To change the particle size distribution, Uniform dispersion of active ingredient.Uniform dispersion of active ingredient.


BindersUsed in tablet formulations to make Used in tablet formulations to make powders powders more compressiblemore compressible and to produce tablets that and to produce tablets that are more resistant to breakage during handling.are more resistant to breakage during handling.In some instances the binding agent imparts In some instances the binding agent imparts viscosity to the granulating solution so that viscosity to the granulating solution so that transfer of fluid becomes difficult.transfer of fluid becomes difficult.This problem can be overcome by adding some This problem can be overcome by adding some or all binding agents in the dry powder prior to or all binding agents in the dry powder prior to granulation.granulation.


Some granulation, when prepared in production Some granulation, when prepared in production sized equipment, take on a dough-like sized equipment, take on a dough-like consistency and may have to be subdivided to a consistency and may have to be subdivided to a more granular and porous mass to facilitate more granular and porous mass to facilitate drying.drying.This can be accomplished by passing the wet This can be accomplished by passing the wet mass through an mass through an oscillating type granulatoroscillating type granulator with with a suitably large screen or a a suitably large screen or a hammer millhammer mill with with either a suitably large screen or no screen at all.either a suitably large screen or no screen at all.


Oscillating type granulatorOscillating type granulatorHammer millHammer mill


Drying The most common conventional method of drying a The most common conventional method of drying a granulation continues to be the granulation continues to be the circulating hot air ovencirculating hot air oven, , which is heated by either steam or electricity.which is heated by either steam or electricity.The important factor to consider as part of scale-up of an The important factor to consider as part of scale-up of an oven drying operation are airflow, air temperature, and oven drying operation are airflow, air temperature, and the depth of the granulation on the trays.the depth of the granulation on the trays.If the granulation bed is too deep or too dense, the drying If the granulation bed is too deep or too dense, the drying process will be inefficient, and if soluble dyes are process will be inefficient, and if soluble dyes are involved, migration of the dye to the surface of the involved, migration of the dye to the surface of the granules.granules.Drying times at specified temperatures and airflow rates Drying times at specified temperatures and airflow rates must be established for each product, and for each must be established for each product, and for each particular oven load.particular oven load.


Fluidized bed dryersFluidized bed dryers are are an attractive alternative to an attractive alternative to the circulating hot air the circulating hot air ovens.ovens.The important factor The important factor considered as part of considered as part of scale up fluidized bed scale up fluidized bed dryer are optimum loads, dryer are optimum loads, rate of airflow, inlet air rate of airflow, inlet air temperature and temperature and humidity.humidity.


Reduction of Particle sizeReduction of Particle sizeCompression factors that may be affected by the particle Compression factors that may be affected by the particle size distribution are size distribution are flowability, compressibility, uniformity flowability, compressibility, uniformity of tablet weight, content uniformity, tablet hardness, and of tablet weight, content uniformity, tablet hardness, and tablet color uniformity.tablet color uniformity.First step in this process is to determine the particle size First step in this process is to determine the particle size distribution of granulation using a series of “stacked” distribution of granulation using a series of “stacked” sieves of decreasing mesh openings.sieves of decreasing mesh openings.Particle size reduction of the dried granulation of Particle size reduction of the dried granulation of production size batches can be carried out by passing all production size batches can be carried out by passing all the material through the material through an oscillating granulatoran oscillating granulator, , a hammer a hammer millmill, a mechanical sieving device, or in some cases, a , a mechanical sieving device, or in some cases, a screening device.screening device.


Oscillating type granulatorOscillating type granulatorHammer millHammer mill


BlendingBlendingType of blending equipment often differs from that using Type of blending equipment often differs from that using in laboratory.in laboratory.In any blending operation, both segregation and mixing In any blending operation, both segregation and mixing occur simultaneously are a function of particle size, occur simultaneously are a function of particle size, shape, hardness, and density, and of the dynamics of shape, hardness, and density, and of the dynamics of the mixing action.the mixing action.Particle abrasion is more likely to occur when high-shear Particle abrasion is more likely to occur when high-shear mixers with spiral screws or blades are used.mixers with spiral screws or blades are used.When a low dose active ingredient is to be blended it When a low dose active ingredient is to be blended it may be sandwiched between two portions of directly may be sandwiched between two portions of directly compressible excipients to avoid loss to the surface of compressible excipients to avoid loss to the surface of the blender.the blender.


Equipments used for mixingEquipments used for mixing

Sigma blade mixer.Sigma blade mixer.

Planetary mixer.Planetary mixer.

Twin shell blender.Twin shell blender.

High shear mixerHigh shear mixer

Planetary mixer


Dry Granulation (sluggingDry Granulation (slugging))A dry powder blend that cannot be directly compressed A dry powder blend that cannot be directly compressed because of poor flow or compression properties.because of poor flow or compression properties.This is done on a tablet press designed for slugging, which This is done on a tablet press designed for slugging, which operates at pressures of about 15 tons, compared with a operates at pressures of about 15 tons, compared with a normal tablet press, which operates at pressure of 4 tons or normal tablet press, which operates at pressure of 4 tons or less.less.Slugs range in diameter from 1 inch, for the more easily Slugs range in diameter from 1 inch, for the more easily slugged material, to ¾ inch in diameter for materials that are slugged material, to ¾ inch in diameter for materials that are more difficult to compress and require more pressure per more difficult to compress and require more pressure per unit area to yield satisfactory compacts.unit area to yield satisfactory compacts.If an excessive amount of fine powder is generated during If an excessive amount of fine powder is generated during the milling operation the material must be screened & fines the milling operation the material must be screened & fines recycled through the slugging operation.recycled through the slugging operation.


Dry CompactionDry CompactionGranulation by dry compaction can also be achieved by Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch.material at pressure of up to 10 tons per linear inch.Materials of very low density require roller compaction to Materials of very low density require roller compaction to achieve a bulk density sufficient to allow encapsulation or achieve a bulk density sufficient to allow encapsulation or compression.compression.One of the best examples of this process is the One of the best examples of this process is the densification of aluminum hydroxide.densification of aluminum hydroxide.Pilot plant personnel should determine whether the final Pilot plant personnel should determine whether the final drug blend or the active ingredient could be more drug blend or the active ingredient could be more efficiently processed in this manner than by conventional efficiently processed in this manner than by conventional processing in order to produce a granulation with the processing in order to produce a granulation with the required tabletting or encapsulation properties.required tabletting or encapsulation properties.


Compression Compression The ultimate test of a tablet formulation and The ultimate test of a tablet formulation and granulation process is whether the granulation can granulation process is whether the granulation can be compressed on a high-speed tablet press.be compressed on a high-speed tablet press.During compression, the tablet press performs the During compression, the tablet press performs the following functions:following functions:

1.1. Filling of empty die cavity with granulation.Filling of empty die cavity with granulation.2.2. Precompression of granulation (optional).Precompression of granulation (optional).3.3. Compression of granules.Compression of granules.4.4. Ejection of the tablet from the die cavity and take-off of Ejection of the tablet from the die cavity and take-off of

compressed tablet.compressed tablet.


Tablet compression machines


HoppeHopperr for holding and feeding granulation to be for holding and feeding granulation to be compressedcompressed

DiesDies that define the size and shape of the tablet that define the size and shape of the tablet PunchesPunches for compressing the granulation within for compressing the granulation within

the diesthe dies Cam tracksCam tracks for guiding the movement of the for guiding the movement of the

punchespunches Feeding mechanismsFeeding mechanisms for moving granulation for moving granulation

from the hopper into the diesfrom the hopper into the dies


Singe punch machine


The compression is applied by the upper punchThe compression is applied by the upper punch Stamping pressStamping press


Singe punch rotary machine

Upper andLower Collar

Collar locker

Singe punch machine

pm3125: lectures 18 to 21

Documents

jomjai peerapattana

khon kaen universityfilm

khon kaen universitylubricants

khon kaen universitysource

khon kaen universitysome

tablet ejection

tablet formulationssource

tablet formulations