Capsules -Pharmaceutics

2. Capsules are solid dosage forms in which one or
more medicinal and/or inert substances are enclosed
within a small shell or container generally prepared
from a suitable form of gelatin.
Depending upon their formulation, the gelatin
capsule shells may be hard or soft.

3. Hard Gelatin Capsulesard Gelatin Capsules
The hard gelatin capsuleThe hard gelatin capsule
consists of a base orconsists of a base or
body and a shorter cap,body and a shorter cap,
which fits firmly over thewhich fits firmly over the
base of the capsulebase of the capsule ..

4. Hard Gelatin Capsulesard Gelatin Capsules
1. Mask the unpleasant tastes of a drug.1. Mask the unpleasant tastes of a drug.
2. Allow powders to be dispensed in an uncompressed2. Allow powders to be dispensed in an uncompressed
form, thus allowing for quicker dissolution andform, thus allowing for quicker dissolution and
absorption of the drug following oral dosingabsorption of the drug following oral dosing
3. Have the flexibility which permit a wide prescribing3. Have the flexibility which permit a wide prescribing
opportunity by the physician in that the pharmacist mayopportunity by the physician in that the pharmacist may
prepare capsules containing a single chemicalprepare capsules containing a single chemical
substance or a combination of drugs at the accuratesubstance or a combination of drugs at the accurate
dosage level for the individual patient.dosage level for the individual patient.
4. Be easier than tablets for some people to swallow.4. Be easier than tablets for some people to swallow.
5. Can alter the release rate of the drug.5. Can alter the release rate of the drug.
Advantage of Hard gelatin capsulesAdvantage of Hard gelatin capsules

5. DisadvantagesDisadvantages or limitations include the followingor limitations include the following ::
1.1. They are subject to the effects of relative humidity andThey are subject to the effects of relative humidity and
to microbial contaminationto microbial contamination ..
2. They may be difficult for some people to swallow2. They may be difficult for some people to swallow ..
3. More expensive (commercially)3. More expensive (commercially) ..

6. Opaque capsules may be prepared by adding anOpaque capsules may be prepared by adding an
insoluble substance as titanium dioxide to the gelatininsoluble substance as titanium dioxide to the gelatin
mixture. Colored, opaque capsules may be prepared bymixture. Colored, opaque capsules may be prepared by
using both a colorant and the opaque-producingusing both a colorant and the opaque-producing
substance.substance.
Gelatin, NF, is a product obtained by partial hydrolysis ofGelatin, NF, is a product obtained by partial hydrolysis of
collagen obtained from the skin, white connective tissue,collagen obtained from the skin, white connective tissue,
and bones of animals.and bones of animals.
It is found in commerce in the form of a fine powder, aIt is found in commerce in the form of a fine powder, a
 The basic empty capsule shellsThe basic empty capsule shells
are made from a mixture of gelatin,are made from a mixture of gelatin,
sugar, and water and are clear,sugar, and water and are clear,
colorless, and essentially tasteless.colorless, and essentially tasteless.
Colorants may be used to prepareColorants may be used to prepare
distinctive capsules.distinctive capsules.

7. depending upon the environmental conditions, independing upon the environmental conditions, in
high humidity, capsules absorb moisture and becomehigh humidity, capsules absorb moisture and become
distorted and lose their rigid shape.distorted and lose their rigid shape.
but in extreme dryness, some of the moisturebut in extreme dryness, some of the moisture
normally present in the gelatin capsules may be lost,normally present in the gelatin capsules may be lost,
and the capsules become brittle and crumble.and the capsules become brittle and crumble.
Thus capsules should be stored in areas of lowThus capsules should be stored in areas of low
humidity.humidity.
Normally, hard gelatin capsulesNormally, hard gelatin capsules
contain between 13 and 16% ofcontain between 13 and 16% of
moisture.moisture.
moisture may be absorbed ormoisture may be absorbed or
released by gelatin capsules,released by gelatin capsules,

8. Gelatin is insoluble in cold water but soluble in hotGelatin is insoluble in cold water but soluble in hot
water, and in gastric fluid where a gelatin capsulewater, and in gastric fluid where a gelatin capsule
rapidly releases its contents.rapidly releases its contents.
Gelatin, being a protein, is digested and absorbed.Gelatin, being a protein, is digested and absorbed.

9. Hard gelatin capsule shells are manufactured mechanical
dipping of manganese bronze pins of the desired shape
and diameter to the desired depth and time into a
reservoir of the melted gelatin mixture, maintained at a
constant temperature to achieve the desired degree of
fluidity.
Then the plate and the pins slowly lifted from the gelatin
bath and gently dried by a flow of temperature and
humidity controlled air

10. Capsule SizesCapsule Sizes
Empty gelatin capsules are manufactured in variousEmpty gelatin capsules are manufactured in various
sizes, varying in length, in diameter, and capacity.sizes, varying in length, in diameter, and capacity.
For human use, empty capsules ranging in size fromFor human use, empty capsules ranging in size from
000 the largest, to 5 the smallest are commercially000 the largest, to 5 the smallest are commercially
available.available.

11. preparation of filled Hard Gelatin Capsulespreparation of filled Hard Gelatin Capsules
The preparation of filled hard gelatin capsules may beThe preparation of filled hard gelatin capsules may be
divided into the following steps:divided into the following steps:
1.1. Preparing the formulationPreparing the formulation
2.2. Selecting the capsule size.Selecting the capsule size.
3. Filling the capsule shells.3. Filling the capsule shells.
4. Cleaning and polishing the filled capsules.4. Cleaning and polishing the filled capsules.

12. Preformulation studies are used to determine if the bulkPreformulation studies are used to determine if the bulk
powders may be blended together as such, or if theypowders may be blended together as such, or if they
require reduction of particle size or processing intorequire reduction of particle size or processing into
formed granules.formed granules.
preparinG tHe formulationpreparinG tHe formulation
MillingMilling
To achieve uniform drug distribution through out aTo achieve uniform drug distribution through out a
powder mix, it is advantageous that the density andpowder mix, it is advantageous that the density and
particle size of the drug and non-drug components areparticle size of the drug and non-drug components are
similar. This is achieved by particle size reductionsimilar. This is achieved by particle size reduction
(milling).(milling).
Dry PowderDry Powder

13. DiluentDiluent
Generally, hard gelatin capsules are used to encapsulateGenerally, hard gelatin capsules are used to encapsulate
between about 65 mg and 1 g of powdered material,between about 65 mg and 1 g of powdered material,
including drug and any di­luent required.including drug and any di­luent required.
If the dose of the drug to be placed in a single capsule isIf the dose of the drug to be placed in a single capsule is
smaller than 65 mg to produce the proper fill, lactose,smaller than 65 mg to produce the proper fill, lactose,
microcrystalline cellulose, and pregelatinized starch aremicrocrystalline cellulose, and pregelatinized starch are
common diluents used in capsule filling. But when thecommon diluents used in capsule filling. But when the
amount of drug is large enough to fill a capsuleamount of drug is large enough to fill a capsule
completely, a diluent may not be required.completely, a diluent may not be required.

14. LubricantLubricant
a lubricant as 1% Magnesium stearate is utilized toa lubricant as 1% Magnesium stearate is utilized to
prevent adhesion and facilitate the flow of the powder inprevent adhesion and facilitate the flow of the powder in
capsule filling machine.capsule filling machine.
GlidantGlidant
The powder mixture or granules must be free-flowing toThe powder mixture or granules must be free-flowing to
allow passage from the hopper by the addition of aallow passage from the hopper by the addition of a
glidant such as 1% silicon dioxide.glidant such as 1% silicon dioxide.
Lubricant and Glidant are used to improve fillingLubricant and Glidant are used to improve filling
properties.properties.

15. Wetting agentWetting agent
Addition wetting agents, as sodium laurylAddition wetting agents, as sodium lauryl
sulfate, in capsule facilitate the wettingsulfate, in capsule facilitate the wetting
of the drug substance by gastrointestinal fluids toof the drug substance by gastrointestinal fluids to
enhance dissolution, and overcome the problemenhance dissolution, and overcome the problem
associated with water-insoluble lubricant asassociated with water-insoluble lubricant as
magnesium stearate which can delay the dissolutionmagnesium stearate which can delay the dissolution
of the drug and its absorption.of the drug and its absorption.

16. Eutectic mixturesEutectic mixtures or mixtures that tend to liquefy, mayor mixtures that tend to liquefy, may
require a diluent or absorbant such as magnesiumrequire a diluent or absorbant such as magnesium
carbonate, kaolin, or light magnesium oxide to separatecarbonate, kaolin, or light magnesium oxide to separate
physically the interacting agents and to absorb anyphysically the interacting agents and to absorb any
liquefied material.liquefied material.
euteCtiC mixtureseuteCtiC mixtures

17. However, some liquids such as fixed or volatile oils thatHowever, some liquids such as fixed or volatile oils that
do not interfere with the stability of the gelatin shells maydo not interfere with the stability of the gelatin shells may
be placed in gelatin capsules which then may be sealedbe placed in gelatin capsules which then may be sealed
to ensure the retention of the liquid (to ensure the retention of the liquid ( soft gelatinsoft gelatin
capsules)capsules)
Gelatin capsules areGelatin capsules are
unsuitable for theunsuitable for the
encapsulation of aqueousencapsulation of aqueous
liquids, because waterliquids, because water
softens the gelatin tosoftens the gelatin to
produce distortion of theproduce distortion of the
capsules.capsules.
LiquidsLiquids

18. SemisolidsSemisolids
This system can be used for bothThis system can be used for both
liquid and solid active ingredients.liquid and solid active ingredients.
Mixtures for filling need only beMixtures for filling need only be
liquid when filled and should beliquid when filled and should be
semisolid after being inside the capsules.semisolid after being inside the capsules.
The materials to be filled must be either thermosofteningThe materials to be filled must be either thermosoftening
or thixotropic in nature to be liquefied by heating oror thixotropic in nature to be liquefied by heating or
shearing forces using heated hopper with a stirrer andshearing forces using heated hopper with a stirrer and
revert to the solid state within the capsule shell.revert to the solid state within the capsule shell.
Used for potent drugs to improve uniformity of filling.Used for potent drugs to improve uniformity of filling.
Used for safely handling toxic drugs to reduceUsed for safely handling toxic drugs to reduce
contamination with filling of powders.contamination with filling of powders.

19. Granules and PelletsGranules and Pellets
Granules are produced byGranules are produced by
granulation and are moregranulation and are more
irregular than pellets whichirregular than pellets which
are spherical andare spherical and
produced byproduced by
microencapsulationmicroencapsulation
Granules and Pellets areGranules and Pellets are
packed in capsules insteadpacked in capsules instead
of powder to produceof powder to produce
modified release patterns.modified release patterns.

20. Capsules within capsules:Capsules within capsules:
Tablets within capsules:Tablets within capsules:
This small tablet can be placed inside the capsule followingThis small tablet can be placed inside the capsule following
the addition of a small quantity of the powder and the fillingthe addition of a small quantity of the powder and the filling
completed.completed.
Small tablets are filled into capsules toSmall tablets are filled into capsules to
produce special release forms or toproduce special release forms or to
separate incompatible ingredients.separate incompatible ingredients.
If one ingredient must be separated fromIf one ingredient must be separated from
others in the formulation, a small capsule,others in the formulation, a small capsule,
such as a No. 5, may be filled with onesuch as a No. 5, may be filled with one
powder and placed into a larger capsulepowder and placed into a larger capsule
with the remaining ingredients in thewith the remaining ingredients in the
formulation.formulation.

21. PowdersPowders GranulesGranules BeadsBeads
TaBleTsTaBleTs CaPsulesCaPsules PasTesPasTes
liquidsliquids

22. The selection of capsule size is best done during theThe selection of capsule size is best done during the
development of the formulation, because the amount ofdevelopment of the formulation, because the amount of
inert materials to be employed is dependent upon the sizeinert materials to be employed is dependent upon the size
or capacity of the capsule to be selected.or capacity of the capsule to be selected.
ii. seleCTion oF CaPsule siZeii. seleCTion oF CaPsule siZe
The density and compressibility of a powder or a powderThe density and compressibility of a powder or a powder
mixture will largely determine to what extent it can bemixture will largely determine to what extent it can be
packed into a capsule shell.packed into a capsule shell.
The amount may vary according to the degree of pressureThe amount may vary according to the degree of pressure
used in filling the capsules.used in filling the capsules.

23. Determination of capsule fill weightDetermination of capsule fill weight
To determine the size of capsule to be used or theTo determine the size of capsule to be used or the
fill weight for a formulation the following relationshipfill weight for a formulation the following relationship
is used:is used:
Capsule fill weight =Capsule fill weight =
Tapped Bulk Density of Formulation X CapsuleTapped Bulk Density of Formulation X Capsule
VolumeVolume

24. ii. FillinG The CaPsule shellsii. FillinG The CaPsule shells
1.1."Punch" Method"Punch" Method
2.2. Hand-Operated Capsule Filling MachinesHand-Operated Capsule Filling Machines
3.3. Automatic-Operated Capsule FillingAutomatic-Operated Capsule Filling
MachinesMachines

25. Used for filling a small number of capsules in theUsed for filling a small number of capsules in the
pharmacy, at the prescription counter.pharmacy, at the prescription counter.
The ingredients are triturated to the same particle sizeThe ingredients are triturated to the same particle size
and then mixed by geometric dilution.and then mixed by geometric dilution.
The powder is placed on a powder paper or ointmentThe powder is placed on a powder paper or ointment
slab and smoothed with a spatula to a heightslab and smoothed with a spatula to a height
approximately half the length of the capsule body.approximately half the length of the capsule body.
"PunCh" MeThod"PunCh" MeThod

26. The base of the capsule is held vertically and the openThe base of the capsule is held vertically and the open
end is repeatedly pushed or "punched" into the powderend is repeatedly pushed or "punched" into the powder
until the capsule is filled;until the capsule is filled;
The cap is then replaced to close the capsule. EachThe cap is then replaced to close the capsule. Each
filled capsule is weighed using an empty capsule as afilled capsule is weighed using an empty capsule as a
counterweight.counterweight.
Powder is added or removed until the correct weight hasPowder is added or removed until the correct weight has
been placed in the capsule.been placed in the capsule.
The filled capsule is tapped so that no air spaces areThe filled capsule is tapped so that no air spaces are
visible within the contents.visible within the contents.

27. Cappunch.rm

28. Pharmacists that prepare capsules on a regular orPharmacists that prepare capsules on a regular or
extensive basis may use hand-operated capsuleextensive basis may use hand-operated capsule
machines.machines.
These machines are available in capacities of 24, 96,These machines are available in capacities of 24, 96,
100, and 144 capsules.100, and 144 capsules.
First, the plates are adjusted to hold the capsule bodiesFirst, the plates are adjusted to hold the capsule bodies
in place while the caps are removed all at one time.in place while the caps are removed all at one time.
The caps remain in place in the top of the machine forThe caps remain in place in the top of the machine for
later use.later use.
hand-oPeraTed CaPsule MaChineshand-oPeraTed CaPsule MaChines

29. Then the plates are adjusted again so that the capsuleThen the plates are adjusted again so that the capsule
bodies will "drop" into place so that the tops are flushbodies will "drop" into place so that the tops are flush
with the working surface of the plate.with the working surface of the plate.
The formulation powder is poured onto the plate andThe formulation powder is poured onto the plate and
special spreaders are used to fill the individualspecial spreaders are used to fill the individual
capsules.capsules.
The combs are used to tamp (compress) and pack theThe combs are used to tamp (compress) and pack the
powder into the capsules.powder into the capsules.
All of the caps are then returned to the capsule bodies,All of the caps are then returned to the capsule bodies,
and the closed capsules are removed from theand the closed capsules are removed from the

31. auToMaTiC-oPeraTed CaPsule FillinG MaChinauToMaTiC-oPeraTed CaPsule FillinG MaChin
Machines developed for industrial use can automaticallyMachines developed for industrial use can automatically
remove the caps from empty capsules, fill the capsules,remove the caps from empty capsules, fill the capsules,
replace the caps, and clean the outside of the capsulesreplace the caps, and clean the outside of the capsules
at a rate of up to 165,000 capsules and greater per hour.at a rate of up to 165,000 capsules and greater per hour.

33. In this process, the two capsule parts are sealed with aIn this process, the two capsule parts are sealed with a
gelatin or polymer band at the joint of the cap and body.gelatin or polymer band at the joint of the cap and body.
A tamper-resistant seal on hard gelatin capsules wasA tamper-resistant seal on hard gelatin capsules was
SEALING of GELAtIN cApSuLESSEALING of GELAtIN cApSuLES
developed in which thedeveloped in which the
contact areas of thecontact areas of the
cap and body arecap and body are
wetted with a mixturewetted with a mixture
of water and ethanol toof water and ethanol to
soften the gelatin andsoften the gelatin and
then thermally bondedthen thermally bonded
at 104° to 113at 104° to 113oo
F toF to
form the seal.form the seal.

34. oNI-SNAp HArd GELAtIN cApSuLEoNI-SNAp HArd GELAtIN cApSuLE
A recent innovation in capsuleA recent innovation in capsule
shellshell
design, where the two halves ofdesign, where the two halves of
thethe
capsule shells are enable to becapsule shells are enable to be
positively joined through lockingpositively joined through locking
grooves in the shell walls.grooves in the shell walls.
The two grooves fit into eachThe two grooves fit into each
otherother
and ensure reliable closing of theand ensure reliable closing of the
filled capsule.filled capsule.

35. V. cLEANING ANd poLISHING tHE fILLEd cApSuLEV. cLEANING ANd poLISHING tHE fILLEd cApSuLE
Capsules prepared on a small scale or on a large scaleCapsules prepared on a small scale or on a large scale
may have small amounts of the powder adhering to themay have small amounts of the powder adhering to the
outside of the capsules.outside of the capsules.
This powder should be removed before packaging orThis powder should be removed before packaging or
dispensing to improve the appearance of the capsules anddispensing to improve the appearance of the capsules and
to preserve their quality of being tasteless onto preserve their quality of being tasteless on
administration. On a large scale, many capsule-fillingadministration. On a large scale, many capsule-filling
machines are affixed with a cleaning vacuum that removesmachines are affixed with a cleaning vacuum that removes
any extraneous material from the capsules.any extraneous material from the capsules.

36. Another proposed cleaning method is to put the capsulesAnother proposed cleaning method is to put the capsules
in a container filled with sodium bicarbonate, sugar, orin a container filled with sodium bicarbonate, sugar, or
sodium chloride, and gently roll the container.sodium chloride, and gently roll the container.
Then the container contents can be poured into a ten-Then the container contents can be poured into a ten-
mesh sieve where the "cleaning salt" will pass through themesh sieve where the "cleaning salt" will pass through the
sieve.sieve.

37. Soft GELAtIN cApSuLESSoft GELAtIN cApSuLES
Soft gelatin capsules (soft elastic gelatin capsules) or (softgels)Soft gelatin capsules (soft elastic gelatin capsules) or (softgels)
are prepared from continuous gelatin shells to which glycerin orare prepared from continuous gelatin shells to which glycerin or
a polyhydric alcohols such as sorbitol has been added to rendera polyhydric alcohols such as sorbitol has been added to render
gelatin elastic or plastic-like.gelatin elastic or plastic-like.
Soft gelatin capsules may be oblong, elliptical (oval), orSoft gelatin capsules may be oblong, elliptical (oval), or
sphericalspherical round, oval, oblong, tube in shape., They may also beround, oval, oblong, tube in shape., They may also be
prepared of single or two-tone color,prepared of single or two-tone color,

38. Application of Soft Gelatin CapsulesApplication of Soft Gelatin Capsules
1. Water immiscible, volatile and nonvolatile liquids such1. Water immiscible, volatile and nonvolatile liquids such
as vegetable and aromatic oils, aromatic and aliphaticas vegetable and aromatic oils, aromatic and aliphatic
hydrocarbons, chlorinated hydrocarbons, ethers, esters,hydrocarbons, chlorinated hydrocarbons, ethers, esters,
alcohols, and organic acids.alcohols, and organic acids.
2. Water miscible, nonvolatile liquids such as2. Water miscible, nonvolatile liquids such as
polyethylene glycols, and nonionic surface activepolyethylene glycols, and nonionic surface active
agents as tween 80.agents as tween 80.
3. Solids may be encapsulated into soft gelatin capsules3. Solids may be encapsulated into soft gelatin capsules
asas
solutions in one of the suitable liquid solvents, assolutions in one of the suitable liquid solvents, as
suspensions, or as dry powders, granules, orsuspensions, or as dry powders, granules, or

39. Liquids which can easily migrate through the
capsule shell cannot be encapsulated into soft
gelatin capsules.
These materials include:
Water, above 5%, and low molecular weight water
soluble and volatile organic compounds such as
alcohols, ketones, acids, amines, and esters.

40. 1.1. They permit liquid medications to become easilyThey permit liquid medications to become easily
portable.portable.
2.2. Comparing the degree of irritation or ulcerogenicComparing the degree of irritation or ulcerogenic
potential of soft gelatin capsule formulations with apotential of soft gelatin capsule formulations with a
tablet formulation, Capsule formulations had a reducedtablet formulation, Capsule formulations had a reduced
ulcerogenic potential when compared to the tabletulcerogenic potential when compared to the tablet
formulation.formulation.
3. Dose uniformity is optimized, because the drug is3. Dose uniformity is optimized, because the drug is
dissolved or dispersed in a liquid which is then doseddissolved or dispersed in a liquid which is then dosed
volumetrically into the capsule accurately.volumetrically into the capsule accurately.
Advantages of Soft Gelatin CapsulesAdvantages of Soft Gelatin Capsules

41. 4. Improve drug stability by resist gaseous diffusion and4. Improve drug stability by resist gaseous diffusion and
contain no water, thus protect drugs sensitive tocontain no water, thus protect drugs sensitive to
oxidation or hydrolysis on long term storage.oxidation or hydrolysis on long term storage.
5. Good bioavailability of drugs than from the commercial5. Good bioavailability of drugs than from the commercial
tablets or capsules, that dissolved or dispersed in atablets or capsules, that dissolved or dispersed in a
water miscible or oily liquids, thus when the capsulewater miscible or oily liquids, thus when the capsule
ingested, the drug dispersed as solution or emulsion toingested, the drug dispersed as solution or emulsion to
give a drug dispersion of high surface areagive a drug dispersion of high surface area

42. prEpArAtIoN of Soft GELAtIN cApSuLESprEpArAtIoN of Soft GELAtIN cApSuLES
In a soft gelatin capsule formulation the medicament is inIn a soft gelatin capsule formulation the medicament is in
solution or is dispersed as a fine suspension in either asolution or is dispersed as a fine suspension in either a
hydrophilic vehicle or a hydrophobic base.hydrophilic vehicle or a hydrophobic base.
Formulation of soft gelatin capsulesFormulation of soft gelatin capsules
There are two main aspects to be considered during theThere are two main aspects to be considered during the
formulation of soft gelatin capsules:formulation of soft gelatin capsules:
The composition of the gelatin shell and the compositionThe composition of the gelatin shell and the composition
of the fill material.of the fill material.

43. The composition of the soft capsule shell consists of twoThe composition of the soft capsule shell consists of two
main ingredients: gelatin and a plasticize (e.g. glycerol).main ingredients: gelatin and a plasticize (e.g. glycerol).
Water is used to form the capsule and it may be desirableWater is used to form the capsule and it may be desirable
or even necessary to add other additives such asor even necessary to add other additives such as
preservatives, dyes, opacifiers and, rarely, flavours andpreservatives, dyes, opacifiers and, rarely, flavours and
drugs.drugs.
Formulation of the gelatin shellFormulation of the gelatin shell

44. To produce shells with a greater flexibility than hard gelatinTo produce shells with a greater flexibility than hard gelatin
capsules it is necessary to control carefully the viscosity andcapsules it is necessary to control carefully the viscosity and
strength of the gelatin used in production.strength of the gelatin used in production.
The mechanical properties of the gelatin shells areThe mechanical properties of the gelatin shells are
controlled by choice of gelatin grade and by adjusting thecontrolled by choice of gelatin grade and by adjusting the
concentration of plasticizer in the shell.concentration of plasticizer in the shell.
GelatinGelatin
If the viscosity of aqueous gelatin solution is too low, aIf the viscosity of aqueous gelatin solution is too low, a
thin,thin,
low strength shell is produced which has the disadvantagelow strength shell is produced which has the disadvantage
ofof
requiring prolonged drying.requiring prolonged drying.
 If the viscosity of the gelatin solution is too high, a thickIf the viscosity of the gelatin solution is too high, a thick
film is produced which may be too hard and brittle. alsofilm is produced which may be too hard and brittle. also
require higher sealing temperatures during manufacture.require higher sealing temperatures during manufacture.

45. The main plasticizer used for soft gelatin capsules isThe main plasticizer used for soft gelatin capsules is
glycerol.glycerol.
Sorbitol and propylene glycol have also been used butSorbitol and propylene glycol have also been used but
they are normally added in combination with glycerol.they are normally added in combination with glycerol.
Plasticizers are added in relatively large concentrations.Plasticizers are added in relatively large concentrations.
The greater the plasticizer content the greater theThe greater the plasticizer content the greater the
flexibility of the shell. (0.3-1.0 parts of dry plasticizer toflexibility of the shell. (0.3-1.0 parts of dry plasticizer to
1 part of dry gelatin).1 part of dry gelatin).
Low ratios 0.3-0.5 are used for oily liquid fills,Low ratios 0.3-0.5 are used for oily liquid fills,
(0.4-0.6) for oily fills with added surfactant,(0.4-0.6) for oily fills with added surfactant,
(0.6-1.0) for water-miscible fills and chewable capsules.(0.6-1.0) for water-miscible fills and chewable capsules.
PlasticizersPlasticizers

46. WaterWater
The demineralized water content of gelatin solution usedThe demineralized water content of gelatin solution used
to produce a soft gelatin capsule shell depends on theto produce a soft gelatin capsule shell depends on the
viscosity of gelatin used (0.7-1.3 parts of water to eachviscosity of gelatin used (0.7-1.3 parts of water to each
part of dry gelatin), 1: 1 ratio being typical.part of dry gelatin), 1: 1 ratio being typical.
PreservativesPreservatives
Preservatives are added to prevent mould growth in thePreservatives are added to prevent mould growth in the
gelatin shell. Potassium sorbitate and methyl, ethyl andgelatin shell. Potassium sorbitate and methyl, ethyl and
propyl hydroxybenzoate (methyl-, ethyl- andpropyl hydroxybenzoate (methyl-, ethyl- and
propylparaben) are common additives.propylparaben) are common additives.

47. ColoursColours
A wide range of colours can be incorporated into softA wide range of colours can be incorporated into soft
gelatin shellsgelatin shells
Water-soluble dyes (synthetic and vegetable), insolubleWater-soluble dyes (synthetic and vegetable), insoluble
inorganic and organic pigments and lakes.inorganic and organic pigments and lakes.
OpacifiersOpacifiers
Titanium dioxide is the most common. It is added inTitanium dioxide is the most common. It is added in
concentrations of about 0-0.5%.concentrations of about 0-0.5%.
Enteric treatmentEnteric treatment
Enteric properties can be imparted to soft gelatin shellsEnteric properties can be imparted to soft gelatin shells
by coating with 4% cellulose acetate phthalate.by coating with 4% cellulose acetate phthalate.

48. Any non-aqueous liquid or powdered solid in suspensionAny non-aqueous liquid or powdered solid in suspension
can be filled into soft gelatin capsules.can be filled into soft gelatin capsules.
It is possible to fill soft gelatin capsules with a very wideIt is possible to fill soft gelatin capsules with a very wide
range of materials.range of materials.
Suspensions, pastes, drugs in solution in either oils,Suspensions, pastes, drugs in solution in either oils,
self-emulsifying oils or water-miscible liquids.self-emulsifying oils or water-miscible liquids.
Formulation of the capsule contentsFormulation of the capsule contents

49. Limitations for fill materialsLimitations for fill materials
Drugs or excipients containing large amounts of water orDrugs or excipients containing large amounts of water or
other gelatin solvents cannot be incorporated.other gelatin solvents cannot be incorporated.
It is not recommended to fill emulsions (whether they beIt is not recommended to fill emulsions (whether they be
o/w or w/o) since they are unstable and will crack as theo/w or w/o) since they are unstable and will crack as the
water is lost from the shell in the manufacturing process.water is lost from the shell in the manufacturing process.
Surfactants may have a deleterious effect on the capsuleSurfactants may have a deleterious effect on the capsule
seal.seal.
Extremes of pH must be avoided. pHs below about 2.5Extremes of pH must be avoided. pHs below about 2.5
attack the gelatin leading to hydrolysis and leakage andattack the gelatin leading to hydrolysis and leakage and
pHs above about 7.5 have a tanning effect on the gelatin,pHs above about 7.5 have a tanning effect on the gelatin,
and affecting the solubility of the shell.and affecting the solubility of the shell.

50. Liquid vehiclesLiquid vehicles
Water-immiscible oils or water-miscible liquids.Water-immiscible oils or water-miscible liquids.
Water-immiscible oils:Water-immiscible oils:
Either volatile or non-volatile oils,Either volatile or non-volatile oils,
Fixed aromatic vegetable oils,Fixed aromatic vegetable oils,
Aliphatic, aromatic and chlorinated hydrocarbons,Aliphatic, aromatic and chlorinated hydrocarbons,
Liquid ethers and esters.Liquid ethers and esters.

51. Water-miscible liquids (hydrophilic)Water-miscible liquids (hydrophilic)
Polyols as Polyethylene glycols with low molecularPolyols as Polyethylene glycols with low molecular
weight (400-600) since they are liquid at ambientweight (400-600) since they are liquid at ambient
temperatures. Alcohols as isopropyl alcohol,temperatures. Alcohols as isopropyl alcohol,
polyglycerols, triacetin, glyceryl esters, sorbitan esters,polyglycerols, triacetin, glyceryl esters, sorbitan esters,
sugar esters and polyglyceryl esters.sugar esters and polyglyceryl esters.
Propylene glycol and glycerol can be used, but thePropylene glycol and glycerol can be used, but the
concentration must be low, (5-10%), in order to preventconcentration must be low, (5-10%), in order to prevent
migration into the gelatin and softening of the shell.migration into the gelatin and softening of the shell.

52. SuspensionsSuspensions
The particle size of the solid should be reduced to lessThe particle size of the solid should be reduced to less
than 180 µm to pass through the filling head.than 180 µm to pass through the filling head.
Insoluble drugs can be dispersed (with suspendingInsoluble drugs can be dispersed (with suspending
agents and surfactants) in the above vehicles oragents and surfactants) in the above vehicles or
combinations of vehicles.combinations of vehicles.
Suspending agentsSuspending agents are added to prevent settling andare added to prevent settling and
maintain homogeneitymaintain homogeneity
• For oily bases (beeswax, paraffin wax, ethylcelluloseFor oily bases (beeswax, paraffin wax, ethylcellulose
and hydrogenated vegetable oil)and hydrogenated vegetable oil)
• For non-oily bases (solid glycol esters as PEG 4000For non-oily bases (solid glycol esters as PEG 4000
andand

53. SurfactantsSurfactants as polysorbate 80 (Tween 80) are oftenas polysorbate 80 (Tween 80) are often
added as wetting agent.added as wetting agent.
Caking of suspensions in soft gelatin capsules can beCaking of suspensions in soft gelatin capsules can be
avoided by rheological control of the vehicle.avoided by rheological control of the vehicle.

54. PreParation of Soft Gelatin CaPSuleSPreParation of Soft Gelatin CaPSuleS

55. PreParation of Soft Gelatin CaPSuleSPreParation of Soft Gelatin CaPSuleS
Soft gelatin capsules may be prepared by:Soft gelatin capsules may be prepared by:
The plate process, using a set of molds to form theThe plate process, using a set of molds to form the
capsules.capsules.
The die processes (rotary or reciprocating processes)The die processes (rotary or reciprocating processes)
more efficient and productive processesmore efficient and productive processes

56.  A warm sheet of gelatin (plain or colored) is placed onA warm sheet of gelatin (plain or colored) is placed on
the bottom plate of the mold.the bottom plate of the mold.
 The liquid medication is poured on it.The liquid medication is poured on it.
 Then a second sheet of the prepared gelatin isThen a second sheet of the prepared gelatin is
carefullycarefully
laid in place on top of the medication, and the toplaid in place on top of the medication, and the top
plateplate
of the mold is put in place.of the mold is put in place.
 The entire mold is then subjected to a press whereThe entire mold is then subjected to a press where
pressure is applied to form, fill, and seal the capsulespressure is applied to form, fill, and seal the capsules
simultaneously.simultaneously.
 The capsules are then removed and washed with aThe capsules are then removed and washed with a
the plate processthe plate process

57.  Liquid gelatin flowing from anLiquid gelatin flowing from an
overhead tank is formed into twooverhead tank is formed into two
continuous ribbons by the rotarycontinuous ribbons by the rotary
die machine and broughtdie machine and brought
together between twin rotatingtogether between twin rotating
dies.dies.
the rotary die processthe rotary die process
 At the same time, metered fill material is injectedAt the same time, metered fill material is injected
between the ribbons at the moment that the dies formbetween the ribbons at the moment that the dies form
pockets of the gelatin ribbons.pockets of the gelatin ribbons.
 These pockets of fill-containing gelatin are thenThese pockets of fill-containing gelatin are then
sealed by pressure and heat.sealed by pressure and heat.
 The soft gelatin capsules may be prepared of singleThe soft gelatin capsules may be prepared of single
or two-tone color, the latter resulting from theor two-tone color, the latter resulting from the
employment of two different colored ribbons of gelatinemployment of two different colored ribbons of gelatin
to form the sides of the capsule.to form the sides of the capsule.

59. ManufaCturinG ProCeSSManufaCturinG ProCeSS

60. •The reciprocating die process is similar to the rotaryThe reciprocating die process is similar to the rotary
process in that ribbons of gelatin are formed and usedprocess in that ribbons of gelatin are formed and used
toto
encapsulate the fill,encapsulate the fill,
•But it differs in that the gelatin ribbons are fed between aBut it differs in that the gelatin ribbons are fed between a
set of vertical dies that continually open and close toset of vertical dies that continually open and close to
formform
rows of pockets in the gelatin ribbons.rows of pockets in the gelatin ribbons.
•These pockets are filled with the medication and areThese pockets are filled with the medication and are
sealed, shaped, and cut out of the film as they progresssealed, shaped, and cut out of the film as they progress
through the machinery.through the machinery.
•As the capsules are cut from the ribbons, they fall intoAs the capsules are cut from the ribbons, they fall into
refrigerated tanks which prevent the capsules fromrefrigerated tanks which prevent the capsules from
The reciprocating die processThe reciprocating die process

61. •Capsules are usually packaged in glass or in plasticCapsules are usually packaged in glass or in plastic
containerscontainers
•Some containing packets of a desiccant to prevent theSome containing packets of a desiccant to prevent the
absorption of excessive moisture by the capsules.absorption of excessive moisture by the capsules.
•Soft capsules have a greater tendency than do hardSoft capsules have a greater tendency than do hard
capsules to soften and adhere to one another, andcapsules to soften and adhere to one another, and
theythey
must be maintained in a cool, dry place.must be maintained in a cool, dry place.