Unit III Tablets

Tablets Tablets &&

CapsulesCapsules

Essential Essential properties of properties of

tabletstabletsAccurate dosageAccurate dosage of medicament, of medicament, uniform in weight, appearance and uniform in weight, appearance and diameterdiameterHave the Have the strengthstrength to withstand the to withstand the rigors of mechanical shocks rigors of mechanical shocks encountered in its production, encountered in its production, packaging, shipping and dispensingpackaging, shipping and dispensingReleaseRelease the medicinal agents in the the medicinal agents in the body in a predictable and reproducible body in a predictable and reproducible mannermannerElegant product, acceptable size and Elegant product, acceptable size and shapeshapeChemical and physical Chemical and physical stabilitiesstabilities

AdvantagesAdvantagesProduction aspectProduction aspect– Large scale production at lowest costLarge scale production at lowest cost– Easiest and cheapest to package and Easiest and cheapest to package and shipship

– High stabilityHigh stabilityUser aspect (doctor, pharmacist, User aspect (doctor, pharmacist, patient)patient)– Easy to handlingEasy to handling– Lightest and most compactLightest and most compact– Greatest dose precision & least Greatest dose precision & least content variabilitycontent variability

– Coating can mark unpleasant tastes & Coating can mark unpleasant tastes & improve patient. acceptabilityimprove patient. acceptability

DisadvantagesDisadvantagesSome drugs resist compression into Some drugs resist compression into dense compactsdense compactsDrugs with Drugs with poor wetting, slow poor wetting, slow dissolution, intermediate to large dissolution, intermediate to large dosages dosages may be difficult or impossible to may be difficult or impossible to formulate and manufacture as a tablet formulate and manufacture as a tablet that provide adequate or full drug that provide adequate or full drug bioavailabilitybioavailabilityBitter taste drugs, drugs with an Bitter taste drugs, drugs with an objectionable odour, or sensitive to objectionable odour, or sensitive to oxygen or moistureoxygen or moisture may require may require encapsulation or entrapment prior to encapsulation or entrapment prior to compression or the tablets may require compression or the tablets may require coating coating

AbsorpAbsorption of tion of drug drug form form

tabletstablets

Ingredients used in Ingredients used in tablet formulationstablet formulationsDrugsDrugs

Fillers, diluent, bulking agentFillers, diluent, bulking agent– To make a reasonably sized tabletTo make a reasonably sized tabletBindersBinders– To bind powders together in the To bind powders together in the wet granulation processwet granulation process

– To bind granule together during To bind granule together during compressioncompression

DisintegrantsDisintegrants– To promote breakup of the tabletsTo promote breakup of the tablets– To promote rapid release of the To promote rapid release of the drugdrug

Lubricants Lubricants – To reduce the friction during tablet To reduce the friction during tablet ejection between the walls of the ejection between the walls of the tablet and the walls of the die cavitytablet and the walls of the die cavity

GlidantsGlidants– Reducing friction between the Reducing friction between the particlesparticles

– To improve the flow properties of To improve the flow properties of the granulations the granulations

AntiadherantsAntiadherants– To prevent adherence of the To prevent adherence of the granules to the punch faces and granules to the punch faces and diesdies

Dissolution (enhancers Dissolution (enhancers and retardants)and retardants)

Wetting agentsWetting agents

Antioxidants Antioxidants

PreservativesPreservatives

Coloring agentsColoring agents

Flavoring agentsFlavoring agents

Types of tabletsTypes of tabletsRoute of administrationRoute of administration– Oral tabletsOral tablets– Sublingual or buccal tabletsSublingual or buccal tablets– Vaginal tabletsVaginal tabletsProduction processProduction process– Compressed tabletsCompressed tablets– Multiple compressed tabletsMultiple compressed tablets

Tablet within a tablets: core Tablet within a tablets: core and shelland shell

Multilayer tabletMultilayer tablet

–Sugar coated tabletsSugar coated tabletsProtect tablets from Protect tablets from moisturemoisture

Mask odor and flavorMask odor and flavorEleganceElegance

–Film coated tabletsFilm coated tabletsThin film coatThin film coatSoluble or insoluble Soluble or insoluble polymer filmpolymer film

–Chewable tabletsChewable tabletsRapid disintegrateRapid disintegrateAntacid, flatulance: rapid Antacid, flatulance: rapid actionaction

Children drugChildren drug–Effervescent tabletsEffervescent tablets

Dissolve in the water Dissolve in the water before drinkbefore drink

Tablet Tablet productionproductionPowders intended for compression Powders intended for compression

into tablets must possess two into tablets must possess two essential propertiesessential properties–Powder fluidityPowder fluidity

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

To produce tablets of a consistent To produce tablets of a consistent weightweight

Powder flow can be improved Powder flow can be improved mechanically by the use of vibrators, mechanically by the use of vibrators, incorporate the glidantincorporate the glidant

–Powder Powder compressibilitycompressibilityThe property of forming a The property of forming a stable, intact compact stable, intact compact mass when pressure is mass when pressure is appliedapplied

Tableting Tableting procedureprocedure

Filling Filling

Compression Compression

EjectionEjection

SCREENINGSCREENINGScreener is an essential part of every Screener is an essential part of every pharmaceutical production process, pharmaceutical production process, particularly as particularly as product quality & product quality & integrityintegrity are so important. The use are so important. The use of a sieve gets rid of of a sieve gets rid of oversized oversized contamination contamination to ensure that to ensure that ingredients & finished products are ingredients & finished products are quality assured during production quality assured during production and before use or despatch.and before use or despatch.

GRANULATIONGRANULATIONGranulation may be defined as a Granulation may be defined as a size size enlargement enlargement process which converts process which converts small particles into physically small particles into physically stronger & stronger & larger agglomerateslarger agglomerates. Granulation method . Granulation method can be broadly classified into two types:-can be broadly classified into two types:-A. WET GRANULATIONA. WET GRANULATIONWet granulation process simply involves Wet granulation process simply involves wet massing wet massing of the powder blend with a of the powder blend with a granulating liquid, wet sizing and drying.granulating liquid, wet sizing and drying.

Wet granulation has Wet granulation has been carried out using,been carried out using,Sigma blade mixer,Sigma blade mixer,Heavy-duty planetary Heavy-duty planetary mixermixer

Sigma blade mixer Planetary mixer

B. DRY GRANULATIONB. DRY GRANULATIONIn dry granulation process the powder In dry granulation process the powder mixture is compressed mixture is compressed without the without the use of heat and solventuse of heat and solvent. It is the least . It is the least desirable of all methods of desirable of all methods of granulation. The two basic granulation. The two basic procedures are to form a compact of procedures are to form a compact of material by compression and then to material by compression and then to mill the compact to obtain a granules.mill the compact to obtain a granules.

DRYINGDRYINGAfter the process of After the process of granulation, product exists granulation, product exists as a as a wet mass wet mass from which from which liquid must be liquid must be removedremoved, , since the presence of water since the presence of water leads to impairment of flow leads to impairment of flow properties. properties.

The essential constituents of an The essential constituents of an effective piece of drying equipment effective piece of drying equipment are a heat supply to increase the are a heat supply to increase the temperature & thereby reduce temperature & thereby reduce relative humidity, a device for relative humidity, a device for removal of evaporated water. The removal of evaporated water. The fluidized bed dryer is the most fluidized bed dryer is the most commonly used device for drying commonly used device for drying tablet granules.tablet granules.

Fluidized bed Fluidized bed dryerdryer

MILLINGMILLINGMilling process is not an easily Milling process is not an easily contained unit operation because of contained unit operation because of the high possibility of cross the high possibility of cross contamination. Whether used to reduce contamination. Whether used to reduce size or distribute colour or active size or distribute colour or active ingredients, milling process is an ingredients, milling process is an integral part of the successful integral part of the successful development & mass production of development & mass production of formulaeformulae

Particle size reduction can Particle size reduction can be carried out by passing be carried out by passing all the material through all the material through an oscillating granulator, a an oscillating granulator, a hammer mill etchammer mill etc

Oscillating type granulator Hammer mill

BLENDINGBLENDINGThe successful The successful mixing of mixing of powderpowder is acknowledged to be is acknowledged to be more difficult unit operation more difficult unit operation because, unlike the situation because, unlike the situation with liquid, perfect with liquid, perfect homogeneity is practically homogeneity is practically requiredrequired

The equipment used for blendingThe equipment used for blending

V- blenderV- blender Double cone blender Double cone blender Ribbon blenderRibbon blender Slant cone blenderSlant cone blender Bin blenderBin blender Orbiting screw blenders vertical Orbiting screw blenders vertical

and horizontal high intensity and horizontal high intensity mixersmixers

V – cone blender Double cone blender

Ribbon blender

COMPRESSIONCOMPRESSION

After the preparation of After the preparation of granules (in case of wet granules (in case of wet granulation) or sized slugs (in case granulation) or sized slugs (in case of dry granulation), they are of dry granulation), they are compressed to get final product. compressed to get final product. The compression is done either by The compression is done either by single punch machine (stamping single punch machine (stamping press) or by multi station machine press) or by multi station machine (rotary press).(rotary press).

The tablet press is a high-speed The tablet press is a high-speed mechanical device. It 'squeezes' mechanical device. It 'squeezes' the ingredients into the required the ingredients into the required tablet shape with extreme tablet shape with extreme precision. It can make the tablet in precision. It can make the tablet in many shapes, although they are many shapes, although they are usually round or oval. Also, it can usually round or oval. Also, it can press the name of the press the name of the manufacturer or the product into manufacturer or the product into the top of the tablet.the top of the tablet.

COATINGCOATING

Coated tablets are defined as tablets Coated tablets are defined as tablets coveredcovered with one or more layers of with one or more layers of mixture of various substances such as mixture of various substances such as natural or synthetic resins, gums, natural or synthetic resins, gums, inactive and insoluble filler, sugar, inactive and insoluble filler, sugar, plasticizer, polyhydric alcohol , waxes, plasticizer, polyhydric alcohol , waxes, authorized colouring material and some authorized colouring material and some times flavoring material. Coating may times flavoring material. Coating may also contain active ingredient.also contain active ingredient.

TYPE OF TABLET COATING PROCESS:-TYPE OF TABLET COATING PROCESS:-

A.SUGAR COATINGA.SUGAR COATING

Compressed tablets may be coated Compressed tablets may be coated with coloured or uncoloured sugar with coloured or uncoloured sugar layer. The coating is water soluble layer. The coating is water soluble and and quickly dissolves after quickly dissolves after swallowingswallowing. The sugar coat . The sugar coat protects protects the enclosed drug the enclosed drug from the from the environment and provides a barrier environment and provides a barrier to objectionable taste or odour.to objectionable taste or odour.

B.FILM COATING--B.FILM COATING--

Film coating is deposition of a thin Film coating is deposition of a thin film of polymer surrounding the film of polymer surrounding the tablet core. Film coating is more tablet core. Film coating is more favoured over sugar coating.favoured over sugar coating.

C.ENTERIC COATING--C.ENTERIC COATING--

This type of coating is used to protect This type of coating is used to protect tablet core from disintegration in the tablet core from disintegration in the acid environment of the stomach.acid environment of the stomach.

PACKAGINGPACKAGING

Pharmaceutical Pharmaceutical manufacturers have to pack manufacturers have to pack their medicines before they their medicines before they can be sent out for can be sent out for distribution. The type of distribution. The type of packaging will depend on the packaging will depend on the formulation of the medicine.formulation of the medicine.

There are generally two types of There are generally two types of packing:-packing:-

1.Strip sealing 2.Blister packing1.Strip sealing 2.Blister packing

'Blister packs' are a common form 'Blister packs' are a common form of packaging used for a wide of packaging used for a wide variety of products. They are safe variety of products. They are safe and easy to use and they allow the and easy to use and they allow the consumer to see the contents consumer to see the contents without opening the pack. without opening the pack.

Many pharmaceutical companies Many pharmaceutical companies use a standard size of blister use a standard size of blister pack. This saves the cost of pack. This saves the cost of different tools and to change the different tools and to change the production machinery between production machinery between products. The blister pack itself products. The blister pack itself must remain absolutely flat as it must remain absolutely flat as it travels through the packaging travels through the packaging processes,processes,

Tablet Tablet compression compression

machinesmachinesHopperHopper for holding and feeding for holding and feeding granulation to be compressedgranulation to be compressed

DiesDies that define the size and shape of that define the size and shape of the tabletthe tablet

PunchesPunches for compressing the granulation for compressing the granulation within the dieswithin the dies

Cam tracksCam tracks for guiding the movement of for guiding the movement of the punchesthe punches

Feeding mechanismsFeeding mechanisms for moving for moving granulation from the hopper into the diesgranulation from the hopper into the dies

Single punch Single punch machinemachine

The compression is The compression is applied by the upper applied by the upper punchpunch

Stamping pressStamping press

Upper andLower Collar

Collar locker

Single Punch Machine (Tablets)

Multi-station Multi-station rotary pressesrotary presses

The head of the tablet machine that The head of the tablet machine that holds the upper punches, dies and holds the upper punches, dies and lower punches in place rotateslower punches in place rotatesAs the head rotates, the punches are As the head rotates, the punches are guided up and down by fixed cam guided up and down by fixed cam tracks, which control the sequence tracks, which control the sequence of filling, compression and ejection. of filling, compression and ejection. The portions of the head that hold The portions of the head that hold the upper and lower punches are the upper and lower punches are called the called the upper an lower turretsupper an lower turrets

The portion holding the dies is The portion holding the dies is called the called the die tabledie table

The The pull down cam (C)pull down cam (C) guides guides the lower punches to the the lower punches to the bottom, allowing the dies to bottom, allowing the dies to overfilloverfill

The punches then pass over a The punches then pass over a weight-control cam (E),weight-control cam (E), which which reduces the fill in the dies to reduces the fill in the dies to the desired amountthe desired amount

A A swipe off blade (D)swipe off blade (D) at the end of at the end of the feed frame removes the excess the feed frame removes the excess granulation and directs it around granulation and directs it around the turret and back into the front of the turret and back into the front of the feed framethe feed frame

The lower punches travel over the The lower punches travel over the lower compression roll (F)lower compression roll (F) while while simultaneously the upper punches simultaneously the upper punches ride beneath the ride beneath the upper compression upper compression roll (G)roll (G)

The upper punches enter a fixed The upper punches enter a fixed distance into the dies, while the lower distance into the dies, while the lower punches are raised to squeeze and punches are raised to squeeze and compact the granulation within the diescompact the granulation within the dies

After the moment of compression, the After the moment of compression, the upper punches are withdrawn as they upper punches are withdrawn as they follow the follow the upper punch raising cam (H)upper punch raising cam (H)

The lower punches ride up the The lower punches ride up the cam (I)cam (I) which brings the tablets flush with or which brings the tablets flush with or slightly above the surface of the diesslightly above the surface of the dies

The tablets strike a sweep off The tablets strike a sweep off blade affixed to the front of blade affixed to the front of the the feed frame (A)feed frame (A) and slide and slide down a chute into a receptacledown a chute into a receptacle

At the same time, the lower At the same time, the lower punches re-enter the punches re-enter the pull pull down cam (C)down cam (C) and the cycle is and the cycle is repeatedrepeated

Although tablet compressing Although tablet compressing machinery has undergone numerous machinery has undergone numerous mechanical modifications over the mechanical modifications over the years, the compaction of materials years, the compaction of materials between a pair of moving punches between a pair of moving punches within a stationary die has within a stationary die has remained remained unchangedunchangedThe principle modification from The principle modification from earlier equipment has been an earlier equipment has been an increase in production rate which is increase in production rate which is regulated by regulated by – Number of tooling setsNumber of tooling sets– Number of compression stationsNumber of compression stations– Rotational speed of the press Rotational speed of the press

Special adaptations of tablet Special adaptations of tablet machines allow for the machines allow for the compression of layered tablets compression of layered tablets and coated tabletsand coated tablets

A device that chills the A device that chills the compression components to allow compression components to allow for the compression of low-for the compression of low-melting point substances such as melting point substances such as waxes i.e. suppositorieswaxes i.e. suppositories

DIFFERENT PUNCHES &DIES

DOUBLE ROTARYMACHINE

UPPER PUNCH AND LOWER PUNCH

Tableting Tableting methodsmethods

Dry methodsDry methods–Direct compressionDirect compression–Dry granulationDry granulation

Wet methodsWet methods–Wet granulationWet granulation

Direct Direct compressioncompression

Tablets are compressed Tablets are compressed directly from powder blends directly from powder blends of the active ingredient and of the active ingredient and suitable excipientssuitable excipients

No pretreatment of the No pretreatment of the powder blends by wet or dry powder blends by wet or dry granulation procedures is granulation procedures is necessarynecessary

AdvantagesAdvantages–EconomyEconomy

Machine: fewer Machine: fewer manufacturing steps and manufacturing steps and pieces of equipmentpieces of equipment

Labor: reduce labor costsLabor: reduce labor costsLess process vallidationLess process vallidationLower consumption of Lower consumption of powerpower

Manufacture of Hard Gelatin Capsules

08 June 200908 June 2009SRTM University, NandedDept. of SRTM University, NandedDept. of

PharmaceuticsPharmaceutics 6060

Manufacture of Hard Manufacture of Hard Gelatin CapsulesGelatin Capsules

1.1.Shell composition :Shell composition :

Gelatin :Gelatin : Prepared by the hydrolysis of Prepared by the hydrolysis of

collagen.collagen. Gelatin in its chemical and Gelatin in its chemical and

physical properties, physical properties, depending upon the source of depending upon the source of the collagen and extraction. the collagen and extraction.

There are two basic types of There are two basic types of gelatin:gelatin:

Type – A and Type – B.Type – A and Type – B. The two types can be The two types can be

differentiated by their differentiated by their isoelectric points (7.0 – 9.0 for isoelectric points (7.0 – 9.0 for type A and 4.8 – 5.0 for type B) type A and 4.8 – 5.0 for type B) and by their viscosity and film and by their viscosity and film forming characteristics.forming characteristics.

Combination of pork skin and Combination of pork skin and bone gelatin are often used to bone gelatin are often used to optimize shell characteristics.optimize shell characteristics.

The physicochemical The physicochemical properties of gelatin of most properties of gelatin of most interest to shell manufactures interest to shell manufactures are the bloom strength and are the bloom strength and viscosity.viscosity.

Colorants :Colorants :Various soluble synthetic dyes (“coal tar Various soluble synthetic dyes (“coal tar

dyes”) and insoluble pigments are used.dyes”) and insoluble pigments are used.Not only play a role in identifying the Not only play a role in identifying the

product, but also may play a role in product, but also may play a role in improving patient compliance.improving patient compliance.

E.g., white, analgesia; lavender, E.g., white, analgesia; lavender, hallucinogenic effects; orange or yellow, hallucinogenic effects; orange or yellow, stimulants and antidepressants.stimulants and antidepressants.

Opaquing agents :Opaquing agents :Titanium dioxide may be included Titanium dioxide may be included

to render the shell opaque.to render the shell opaque.Opaque capsules may be employed Opaque capsules may be employed

to provide protection against light to provide protection against light or to conceal the contents.or to conceal the contents.

Preservatives :Preservatives :When preservatives are employed, When preservatives are employed,

parabens are often selected.parabens are often selected.

Shell manufacture Shell manufacture



I. Dipping : Pairs of the stainless steel pins are dipped into the dipping

solution to simultaneously form the caps and bodies. The pins are at ambient temperature; whereas the dipping

solution is maintained at a temperature of about 500C in a heated, jacketed dipping pan.

The length of time to cast the film has been reported to be about 12 sec.

II. Rotation : After dipping, pins are elevated and rotated 2-1/2 times

until they are facing upward. This rotation helps to distribute the gelatin over the pins

uniformly and to avoid the formation of a bead at the capsule ends.



III.III.DryingDrying : : The racks of gelatin coated pins then pass The racks of gelatin coated pins then pass

into a series of four drying oven.into a series of four drying oven. Drying is mainly done by dehumidification.Drying is mainly done by dehumidification. A temperature elevation of only a less A temperature elevation of only a less

degrees is permissible to prevent film degrees is permissible to prevent film melting.melting.

Under drying will leave the films too sticky Under drying will leave the films too sticky for subsequent operation.for subsequent operation.

IV.IV.StrippingStripping : : A series of bronze jaws strip the cap and A series of bronze jaws strip the cap and

body portions of the capsules from the body portions of the capsules from the pins.pins.



V.V. TrimmingTrimming : : The stripped cap and body portions The stripped cap and body portions

are delivered to collects in which they are delivered to collects in which they are firmly held.are firmly held.

As the collects rotate, knives are As the collects rotate, knives are brought against the shells to trim brought against the shells to trim them to the required length.them to the required length.

VI.VI.JoiningJoining : : The cap and body portions are aligned The cap and body portions are aligned

concentrically in channels and the two concentrically in channels and the two portions are slowly pushed together.portions are slowly pushed together.



3)3)Sorting :Sorting : The moisture content of the capsules as they The moisture content of the capsules as they

are from the machine will be in the range of 15 – are from the machine will be in the range of 15 – 18% w/w.18% w/w.

During sorting, the capsules passing on a During sorting, the capsules passing on a lighted moving conveyor are examined visually lighted moving conveyor are examined visually by inspectors.by inspectors.

Defects are generally classified according to Defects are generally classified according to their nature and potential to cause problems in their nature and potential to cause problems in use.use.

4)4)Printing :Printing : In general, capsules are printed before filling.In general, capsules are printed before filling. Generally, printing is done on offset rotary Generally, printing is done on offset rotary

presses having throughput capabilities as high presses having throughput capabilities as high as 3-quarter million capsules/hr as 3-quarter million capsules/hr



Size Volume Fill weight(g) at 0.8 g/cm3 powder density

000 1.37 1.096

00 0.95 0.760

0 0.68 0.544

1 0.50 0.400

2 0.37 0.296

3 0.30 0.240

4 0.21 0.168

5 0.15 0.104

5) Sizes and shapes : For human use, empty gelatin capsules are

manufactured in eight sizes, ranging from 000 to 5. Capsule capacities in table:



The largest size normally acceptable to The largest size normally acceptable to patient is a No: 0.patient is a No: 0.

Three larger size are available for veterinary Three larger size are available for veterinary use: 10, 11, and 12 having capacities of use: 10, 11, and 12 having capacities of about 30, 15, and 7.5 g, respectively.about 30, 15, and 7.5 g, respectively.

The standard shape of capsules is The standard shape of capsules is traditional, symmetrical bullet shape.traditional, symmetrical bullet shape.

Some manufactures have employed Some manufactures have employed distinctive shapes.distinctive shapes.

e.g. Lilly’s pulvulee.g. Lilly’s pulvule tapers to a bluntly tapers to a bluntly pointed end.pointed end.

Smith Kline Beacham’s spansule capsulesSmith Kline Beacham’s spansule capsules taper at taper at

both the cap and body ends.both the cap and body ends.



6)6)Sealing :Sealing : Capsules are sealed and somewhat Capsules are sealed and somewhat

reshaped in the Etaseal process.reshaped in the Etaseal process. This thermal welding process forms an This thermal welding process forms an

indented ring around the waist of the indented ring around the waist of the capsule where the cap overlaps the body.capsule where the cap overlaps the body.

7)7)Storage :Storage : Finished capsules normally contain an Finished capsules normally contain an

equilibrium moisture content of 13-16%.equilibrium moisture content of 13-16%. To maintain a relative humidity of 40-To maintain a relative humidity of 40-

60% when handling and storing capsules.60% when handling and storing capsules.



Filling of hard gelatin Filling of hard gelatin capsulescapsules

Equipment used in capsule filling Equipment used in capsule filling operations involves one often of two operations involves one often of two types of filling systems.types of filling systems.

Zanasi or Martelli encapsulator: Zanasi or Martelli encapsulator: Forms slugs in a dosatar which is a Forms slugs in a dosatar which is a

hollow tube with a plunger to eject hollow tube with a plunger to eject capsule plug.capsule plug.

Hofliger-Karg machine:Hofliger-Karg machine:Formation of compacts in a die plate Formation of compacts in a die plate

using tamping pins to form a compact.using tamping pins to form a compact.



HOFLIGER KARG AUTOMATICCAPSULE FILLING MACHINE

ZANASI AUTOMATICCAPSULE FILLING MACHINE



In this both system, the scale-up In this both system, the scale-up process involve bulk density, powder process involve bulk density, powder flow, compressibility, and lubricant flow, compressibility, and lubricant distribution.distribution.

Overly lubricated granules are Overly lubricated granules are responsible for delaying capsule responsible for delaying capsule disintegration and dissolution.disintegration and dissolution.



OSAKA MODEL R-180 SEMI AUTOMATIC CAPSULE

FILLING MACHINE



Manufacture of Soft Gelatin Manufacture of Soft Gelatin CapsulesCapsules

I.I. Composition of the shell:Composition of the shell: Similar to hard gelatin shells, the basic Similar to hard gelatin shells, the basic

component of soft gelatin shell is gelatin; component of soft gelatin shell is gelatin; however, the shell has been plasticized.however, the shell has been plasticized.

The ratio of dry plasticizer to dry gelatin The ratio of dry plasticizer to dry gelatin determines the “hardness” of the shell and determines the “hardness” of the shell and can vary from 0.3-1.0 for very hard shell to can vary from 0.3-1.0 for very hard shell to 1.0-1.8 for very soft shell.1.0-1.8 for very soft shell.

Up to 5% sugar may be included to give a Up to 5% sugar may be included to give a “chewable” quality to the shell.“chewable” quality to the shell.

The residual shell moisture content of finished The residual shell moisture content of finished capsules will be in the range of 6-10%.capsules will be in the range of 6-10%.



II.II. Formulation :Formulation : Formulation for soft gelatin capsules involves Formulation for soft gelatin capsules involves

liquid, rather than powder technology. liquid, rather than powder technology. Materials are generally formulated to produce Materials are generally formulated to produce

the smallest possible capsule consistent with the smallest possible capsule consistent with maximum stability, therapeutic effectiveness maximum stability, therapeutic effectiveness and manufacture efficiency.and manufacture efficiency.

The liquids are limited to those that do not The liquids are limited to those that do not have an adverse effect on gelatin walls.have an adverse effect on gelatin walls.

The pH of the lipid can be between 2.5 and The pH of the lipid can be between 2.5 and 7.5.7.5.

Emulsion can not be filled because water will Emulsion can not be filled because water will be released that will affect the shell.be released that will affect the shell.



The types of vehicles used in soft gelatin The types of vehicles used in soft gelatin capsules fall in to two main groups:capsules fall in to two main groups:

1.1. Water immiscible, volatile or more likely more Water immiscible, volatile or more likely more volatile liquids such as vegetable oils, mineral volatile liquids such as vegetable oils, mineral oils, medium-chain triglycerides and oils, medium-chain triglycerides and acetylated glycerides.acetylated glycerides.

2.2. Water miscible, nonvolatile liquids such as Water miscible, nonvolatile liquids such as low molecular weight PEG have come in to low molecular weight PEG have come in to use more recently because of their ability to use more recently because of their ability to mix with water readily and accelerate mix with water readily and accelerate dissolution of dissolved or suspended drugs. dissolution of dissolved or suspended drugs.

All liquids used for filling must flow by gravity All liquids used for filling must flow by gravity at a temperature of 35at a temperature of 3500c or less.c or less.

The sealing temperature of gelatin films is 37-The sealing temperature of gelatin films is 37-404000C.C.



III.III.Manufacture process :Manufacture process :

A.A. Plate process :Plate process :

The process involved The process involved Placing the upper half of a plasticized Placing the upper half of a plasticized

gelatin sheet over a die plate containing gelatin sheet over a die plate containing numerous die pockets,numerous die pockets,

Application of vacuum to draw the sheet in Application of vacuum to draw the sheet in to the die pockets, to the die pockets,

Filling the pockets with liquor or paste,Filling the pockets with liquor or paste, Folding the lower half of gelatin sheet back Folding the lower half of gelatin sheet back

over the filled pockets, andover the filled pockets, and Inserting the “ sandwich” under a die press Inserting the “ sandwich” under a die press

where the capsules are formed and cut out.where the capsules are formed and cut out.



B.B. Rotary die press:Rotary die press: In this process, the die cavities are machined In this process, the die cavities are machined

in to the outer surface of the two rollers. in to the outer surface of the two rollers. The die pockets on the left hand roller form The die pockets on the left hand roller form

the left side of the capsule and the die the left side of the capsule and the die pockets on the right hand roller form the pockets on the right hand roller form the right side of the capsule.right side of the capsule.

Two plasticized gelatin ribbons are Two plasticized gelatin ribbons are continuously and simultaneously fed with the continuously and simultaneously fed with the liquid or paste fill between the rollers of the liquid or paste fill between the rollers of the rotary die mechanism.rotary die mechanism.

As the die rolls rotate, the convergence of As the die rolls rotate, the convergence of the matching die pockets seals and cuts out the matching die pockets seals and cuts out the filled capsules.the filled capsules.



08 June 08 June 20092009

SRTM SRTM University, University,

NandedDept. NandedDept. of of

PharmaceutiPharmaceuticscs 8383

C.C. Accogel process:Accogel process: In general, this is another rotary process In general, this is another rotary process

involving involving A measuring roll,A measuring roll, A die roll, andA die roll, and A sealing roll.A sealing roll.

As the measuring roll and die rolls rotate, the As the measuring roll and die rolls rotate, the measured doses are transferred to the gelatin-measured doses are transferred to the gelatin-linked pockets of the die roll.linked pockets of the die roll.

The continued rotation of the filled die The continued rotation of the filled die converges with the rotating sealing roll where a converges with the rotating sealing roll where a second gelatin sheet is applied to form the second gelatin sheet is applied to form the other half of the capsule.other half of the capsule.

Pressure developed between the die roll and Pressure developed between the die roll and sealing roll seals and cuts out the capsules.sealing roll seals and cuts out the capsules.



4.4.Bubble method:Bubble method: The Globex Mark II The Globex Mark II

capsulator produces truly capsulator produces truly seamless, one-piece soft seamless, one-piece soft gelatin capsules by a gelatin capsules by a “bubble method”.“bubble method”.



A concentric tube dispenser simultaneously A concentric tube dispenser simultaneously discharges the molten gelatin from the outer discharges the molten gelatin from the outer annulus and the liquid content from the tube.annulus and the liquid content from the tube.

By means of a pulsating pump mechanism, By means of a pulsating pump mechanism, the liquids are discharged from the the liquids are discharged from the concentric tube orifice into a chilled-oil concentric tube orifice into a chilled-oil column as droplets that consists of a liquid column as droplets that consists of a liquid medicament core within a molten gelatin medicament core within a molten gelatin envelop.envelop.

The droplets assume a spherical shape under The droplets assume a spherical shape under surface tension forces and the gelatin surface tension forces and the gelatin congeals on cooling.congeals on cooling.

The finished capsules must be degreased and The finished capsules must be degreased and dried.dried.



IV.IV. Soft/Liquid-filled hard gelatin capsules:Soft/Liquid-filled hard gelatin capsules: Important reason: the standard for liquid Important reason: the standard for liquid

filled capsules was inability to prevent filled capsules was inability to prevent leakage from hard gelatin capsules.leakage from hard gelatin capsules.

As banding and of self-locking hard gelatin As banding and of self-locking hard gelatin capsules, together with the development of capsules, together with the development of high-resting state viscosity fills, has now high-resting state viscosity fills, has now made liquid/semisolid-filled hard gelatin made liquid/semisolid-filled hard gelatin capsules.capsules.

As with soft gelatin capsules, any materials As with soft gelatin capsules, any materials filled into hard capsules must not dissolve, filled into hard capsules must not dissolve, alter or otherwise adversely affect the alter or otherwise adversely affect the integrity of the shell.integrity of the shell.

Generally, the fill material must be pumpable.Generally, the fill material must be pumpable.



Three formulation strategies based on having a Three formulation strategies based on having a

high resting viscosity after filling have been high resting viscosity after filling have been

described.described.

1.1. Thixotropic formulations,Thixotropic formulations,

2.2. Thermal-setting formulations,Thermal-setting formulations,

3.3. Mixed thermal-Thixotropic systems.Mixed thermal-Thixotropic systems.

The more lipophilic contents, the slower the The more lipophilic contents, the slower the

release rate.release rate.

Thus, by selecting excipients with varying HLB Thus, by selecting excipients with varying HLB

balance, varying release rate may be achieved.balance, varying release rate may be achieved.



CAPSULE POLISHING MACHINE

AUTO MATIC CAPSULE

ARRANGEMNT

Unit III Tablets

Documents

fluidized

sigma blade

die rolls

single punch

soft gelatin

hard gelatin

feed frame

die roll