The document provides information about capsules, including definitions, history, types (hard capsules, soft gelatin capsules, microencapsulation), and methods of preparation. It discusses the key components of capsules (gelatin, colorants, preservatives), as well as the processes involved in manufacturing hard and soft gelatin capsules. The summary highlights the document's focus on capsules as a solid dosage form where active ingredients are enclosed in gelatin shells for oral administration, and methods for filling capsules with various materials like powders, semisolids, and liquids.

1. ECZANES PHARMACEUTICALS
SUBMITTED TO: SIR ZEESHAAN
Capsules assignment
CAPSULES
ASSIGNMENT BY
ECZANES
2/15/2016

2. ECZANE MEMBERS:
1. SYEDA AZKA WASE’
PharmD
2nd
professional
D14M29
2. AREEBA ZAIN
PharmD
2nd
professional
D14M51
3. FARYAL JAVAID
PharmD
2nd
professional
D14M49
4. MOEEZA SADDIQUE
PharmD
2nd
professional
D14M87
5. FARWA ARJUMAND
PharmD
2nd
professional
D14M109

3. CONTENTS OF ASSIGNMENT:
1) Introduction
2) Definition
3) History
4) Types
5) Methodsof preparationsof hard gelatin
6) Methodsof preparationsof soft gelatin
7) Introductionof microencapsulation
8) Advantages and disadvantages
9) Pharmaceuticalapplications
10) Quality control tests
11) Quality control management
12) Compendialrequirementsof capsules
13) Storage
14) Packaging
15) Distribution

4. CAPSULES
Definition:
Capsules are solid dosage form of medication in which the drug is enclosed in either a hard or soft soluble
container or shell made of gelatin. It is also defined as dosage forms in which one or more medicinal or
inert substances are enclosed within a small gelatin shell. Most are intended to be swallowed whole, but
occasionally the contents may be removed from the gelatin shell and employed as a premeasured
medicinal powder.
Major preferences of capsules:
1. Tastelessness
2. Ease of administration
3. Easily filled either extemporaneously or in commercial scale
4. Permit physician to prescribe the exact medication needed by the patient
5. Eliminate the presence of numerous additives, as in the case of tablets which may influence the
absorption of the drug and therefore the clinical absorption obtained.
6. Preferred method for administering new therapeutics for evaluation in initial clinical trials.
7. Preference of some patients for capsules
General History of capsule medication:
In 1834, Mothes and Dublanc were granted a
patent for a method to produce a single-piece
gelatin capsule that was sealed with a drop of
gelatin solution. They used individual iron molds
for their process, filling the capsules individually
with a medicine dropper. Later on, methods
were developed that used sets of plates with
pockets to form the capsules. Although some
companies still use this method, the equipment
is not produced commercially any more.
Figure: capsule)
Types of capsules:
There are followingthree typesof capsule medicinesbeingadministered:

5. 1- Hard capsules
2- Softgelatincapsules
3- Microencapsulation
1. HARD CAPSULES:
History:
Mothesand Dublanc,twoFrenchmen,are generallycreditedwith the
inventionof the gelatincapsule.Theirpatents,grantedinMarchand
Decemberof 1834, covereda methodforproducingsingle-piece,
olive-shaped,gelatincapsules, whichwere closedafterfillingbya
drop of concentratedwarmgelatinsolution.The twopiece
telescopingcapsule,inventedbyJamesMurdockof London(1848), was
patentedinEnglandin1865.
Definition:
The majorityof capsule productsare made of hard gelatincapsules.Hardgelatincapsulesare made of twoshells:the
capsule bodyanda shortercap. The cap fitssnuglyoverthe openendof the capsule body.The basichard gelatin
capsule shellsare made frommixturesof gelatin,sugar,andwater.Theyare clear,colorless,andessentiallytasteless.
Gelatin:
 Gelatinisa productobtainedbypartial hydrolysisof collagenacquiredfromthe skin,white connectivetissue,
and bonesof animals.Gelatinisaproteinwhichissolubleinwarm(orhot) water, but insoluble incoldwater.
At lowtemperatures,gelatindissolvedinwaterbecomesagel (whichisinsoluble inwater).Thispropertyis
usedto prepare Jellyandothergelatindeserts.Gelatincapsulesbecomedissolvedinwarmgastricfluidand
release the medicament.
 Two recentdevelopmentshave takenplace inthe gelatinsupplyarea.First,“green”(fresh)bonesare being
usedcommerciallyasasource of Type-Bgelatin.Aside fromadditional pretreatmenttoremove residual
tissuesandfat,the processingcoincideswiththatusedforagedbines,andthe gelatinsobtainedare
indistinguishable fromeachotherinpractical use.
 The seconddevelopmentisthe processingof an“acid-bone”gelatinpreparedfrombone bytechniques
essentiallycomparable tothose forType-A gelatins.The resultinggelatinshowsanalteredisoelectricpoint
(pH 5.5-6.0), andgenerally,intermediatephysical characteristicsforthe film.The acidextractiontechnique
for bonesisvaluable toprocessorsof gelatinbecauseof the decreasedextractiontimerequires.
Amounts:
Normally,hardgelatincapsulescontain13–16% of moisture.If additional moisture isabsorbedwhenstored
ina highrelative humidityenvironment,hardgelatincapsule shell maylose theirrigidshape andbecome
distorted.Inanopposite environmentof extremedryness,capsulesmaybecome toobrittle andmaycrumble
duringhandling.Since moisture canbe absorbedorreleasedbythe gelatincapsules,capsulescontaining
moisture-sensitivedrugsare usuallypackaged incontainers.Gelatinformakinghardshellsisof bone origin
and has 220–280 g bloomstrength(the weightrequiredtodepressastandardplunger4 mm intothe gel).

6. METHODS OF PEPRARTION FOR CAPSULES:
Raw material:
Raw MaterialsforCapsulesThe rawmaterialsusedinthe manufacture of bothhard andsoft gelatincapsulesare
similar.Bothcontain
 gelatin
 water
 colorants
 Optional materialssuchasprocessaidsandpreservatives.
1. Gelatin:
Gelatinisthe major componentof the capsulesand hasbeenthe material fromwhichtheyhave traditionally
beenmade.
2. Colorants:
The color of pharmaceutical productplaysan importantrole intheiruse.Colorisusedprincipallytoidentifya
productin all stagesof its manufacture anduse.The colorantsthat can be usedincapsulesare of twotypes:
i. watersoluble dyes
ii. insoluble pigments
Three mostcommonlyuseddyesare
 erythrosine
 indigocarmine
 quinolineyellow.
3. preservativesandsurfactant:
Preservativesandsurfactantsare addedto the gelatinsolutionduringcapsule manufacture toaidinprocessing.
Gelatinsolutionsare anideal mediumforbacterial growthattemperaturesbelow 55‘C. Materialsusedas
preservativesinclude:
 sulfurdioxidewhichisaddedasthe sodiumsaltsbisulfite
 meta bisulfite
 ascorbic acid
 the methyl propyl estersof parahydroxyl benzoicacid,
 organic acids
 benzoicacid
 propanoicacids
Methodof production of emptyhard gelatinshells:
The metal moldsat roomtemperature are dippedintoahot
gelatinsolution,whichgelstoformafilm.Thisisdried,cutto
length,removedfromthe moundsandthe twopartsare
joinedtogether,these processesare carriedoutasa
continuousprocessin large machines.
The completelyautomaticmachine mostcommonlyusedfor
capsule productionconsistsof mechanismsforautomatically
dipping,spinning,drying,stripping,trimming,andjoiningthe
capsules.
 Stainlesssteel pinsare usedonwhichthe capsule is
formedandcontrolsdimensionsof the capsule.
 One hundredandfiftypairsof these pinsare dippedintogelatinsol of carefullycontrolledviscositytoform
caps and bodiessimultaneously.The pinsare usuallyrotatedtodistribute the gelatinuniformly,duringwhich
time the gelatinmaybe setor gelledbya blastof cool air.

7. degriesed
dried/crushed
bone
acid treatment lime treatment washing acid treatment
multiple hot
water
extraction
filtration
ion exchange
deionozation
evaporationfiltration
final
concentration
sterilization
polishfiltration
chillingto set
point
extrusion drying miling
blendingn
packaging
 The pinsare movedthrougha seriesof controlledairdryingkilnsforthe gradual andpreciselycontrolled
removal of water.
 The capsulesare stripedfromthe pinsby bronze jawsandtrimmedtolengthbystationarykniveswhile the
capsule halvesare beingspuninchunksorcollets.
 Afterbeingtrimmedtoexactlength,the capandbodysectionsare 6 joinedandejectedfromthe machine.
The entire cycle of the machine lasts approximately45min.
 Thicknessof the capsule wall iscontrolledbythe viscosityof the gelatinsolutionandthe speedandtime of
dipping.Moldpindimensions,precisedrying,andmachine control relatingtocutlengthsare mattersthat
are critical to the final dimensions.
Types of capsule filling materials:
Typesof materialsforfillingintohardgelatincapsules:
i. Dry solids – powders,pellets,granulesortablets
ii. Semisolids –suspensionsorpastes
iii. Liquids – non-aqueousliquids
1. Fillingcapsuleswitha semisolidmass:
If the material tobe placedintohard gelatincapsulesisasemisolid,itcanbe encapsulatedbyeitherformingapipe
or pouringa melt.
 Pipe:
If the material issufficientlyplastic,itcanbe rolledintoapipe witha diameterslightlylessthanthatof the inner
diameterof the capsule inwhichitwill be enclosed.The desiredquantityof material iscutusinga spatulaor knife,
the lengthdeterminingthe weightof the material enclosed.The piecesmaybe dustedwithcornstarch(check
patientallergies) priortoindividual insertionintothe capsules.If amaterial istoofluidtobe workedasdescribed,it
may be necessarytoadd cornstarch or some similarmaterial toyieldamore firmconsistency.The quantitytobe
addedcan be determinedempirically.
 Semisolidpour:
If the material istoofirmto roll intoa pipe butits meltingpointissatisfactory,itcanbe meltedandpouredintothe
capsule bases,cooled,andthe capsreplaced.A standto holdthe capsule bodiesmaybe fashionedfromablockof
woodintowhicha seriesof holesthe diameterof the capsule capsisdrilled.Whencapsule capsare gluedintothese
holes,capsule basesmaybe insertedforfillingwithoutscratchingormarkingbythe wood. Thismethodalsocan be
usedto enhance the bioavailabilityof drugs,whichare poorlysolubleandexhibitbioavailabilityproblems.Forthis
purpose,the drugisaddedto a meltof a material suchas polyethylene glycol (PEG).The mixture isheatedand

8. stirreduntil the powderiseithermeltedorthoroughlymixedinthe PEG.The meltiscooledtojustabove the melting
pointof the PEG and pouredintothe capsule shellsasdescribed.Whenthismethodisused,the desiredquantities
can be measuredusingapipet,syringe,orcalibrateddroppertodeliverthe volumetothe individual capsules.
2. Liquidsin Hard GelatinCapsules :
Liquidscanbe preparedinhardgelatincapsulesif the gelatinisnotsoluble inthe liquidtobe encapsulated;alcoholic
solutionsandfixedandvolatileoilsworkwell.Itmaybe necessarytodetermine the solubilityof gelatininthe liquid
by experimentation.The liquidcanbe measuredaccuratelyusingapipette (micropipet) oracalibrateddropperand
droppedintothe gelatinbase,takingcare notto touchthe opening.The gelatincapscan be touched,openend
down,ona moisttowel tosoftenthe gelatinatthe openingof the capsor a cottonswabdippedinwarmwatercan
be rubbedaroundthe edge of the capsule capto soften.The cap isplacedoverthe base containingthe liquidwitha
slighttwistandthe softenededge of the capshouldforma seal withthe base to preventleakage.Priortopackaging,
these capsulesshouldbe placedonaclean,drysheetof paperand observedforleakage.Anothermethodof sealing
makesuse of a warmgelatinsolutionthatispaintedaroundthe capsulesandthe insideof the capsprior to placing
on the base.
Industrial scale filling
The machinesforindustrial -scale fillingof hard gelatin
capsulescome ingreatvarietyof shapesand sizes,varying
fromsemi- tofullyautomaticandranginginoutputfrom
5000 to 15000 perhour.Automaticmachinescanbe either
continuousinmotion,likearotary tabletpress,or
intermittent,wherethe machine stopstoperformafunction
and thenindexesroundtothe nextpositiontorepeatthe
operationona furthersetof capsules.
Types of excipientsusedinpowder-filledcapsules
 Diluents– diluentsare the excipientsthatare usually
presentinthe greatestconcentrationinaformulation
and theymake upthe necessarybulkwhenthe quantityof the active ingredientisinsufficienttomake upthe
requiredbulke.gLactose,maize starch,calciumsulfate etc.
 Lubricants and Glidants – whichreduce powdertometal adhesionandpromote flow propertieseg.
Magnesiumstearate,talc.

9.  Wettingagents – whichimprove waterpenetrationforpoorlysoluble drugseg.Sodiumlaurylsulfate
 Disintegrants – whichproduce disruptionof the powdermasscrospovidone,sodiumstarchglycolate.
Cleaningand Packaging
It is imperativethateveryprecautiontominimizetracesof moisture orbodyoilsoncapsulesbe takentoreduce
powdersstickingtothe surface,whichwouldcreate disagreeable appearance andtaste.Cleaningcapsulesisdifficult
if theyhave become moistorsticky.The capsulesshouldbe handledsothattheyretaintheirdrynessandshiny
appearance.Use of glovesprovidesamore hygienicenvironmentandhelpspreservethe dry,shinycapsule
appearance.Anoldmethod,where glovesare unavailable,is:
(1) Wash anddry handsthoroughly,
(2) Keepthe fingersdrybythe frictionof a towel thatis strippedthroughthe tightlyclenchedfingersuntil aclearly
perceptibleheatisgenerated,
(3) Fouror five capsulesmaybe preparedbefore there will be aneedtorepeatthe process.
Advantages:
1. Elegance,ease of use andportability,
2. Capsuleshave become apopulardosage formbecause theyprovideasmooth,slippery,easilyswallowed
and tastelessshell fordrugs
3. Theyare particularlybeneficial fordrugshavinganunpleasanttaste orodor.
Disadvantages:
1. Capsulesare notusuallyusedforthe administrationof extremelysoluble materialssuchas
potassiumchloride,potassiumbromide,orammoniumchloride since the suddenrelease of such
compoundsinthe stomachcouldresultinirritatingconcentrations.
2. Capsulesshouldnotbe usedforhighlyefflorescentordeliquescentmaterials.Efflorescentmaterials
may cause the capsulestosoften,whereasdeliquescentpowdersmaydrythe capsule shell to
excessivebrittleness.Insome cases,thisdehydrationmaybe retardedorpreventedbythe use of
small amountsof inertoilsinthe powdermixture.
SOFTGELATIN CAPSULES:
A softgel is an oral dosage form for medicine similar to capsules. They consist of a gelatin based shell
surrounding a liquid fill. Soft gel shells are a combination of gelatin, water, opacifier and a plasticizer such
as glycerin or sorbitol.
Softgelatin(alsocalledsoftgel orsoftelastic) capsulesconsistof onepiece hermetically-sealedsoftshells.Softgelatin
capsulesare preparedbyaddinga plasticizer,suchasglycerinorpolyhydricalcohol (e.g.,sorbitol),togelatin.The
plasticizermakesgelatinelastic.Softgelatincapsulescome invariousshapessuchasspherical,elliptical,oblong,and
special tube shapeswithandwithouttwistoff.Theycancontainnon-aqueousliquids,suspensions,pastymaterials,or
dry powders.Theyare especiallyimportanttocontainvolatiledrugsubstancesordrugmaterialssusceptibleto
deteriorationinthe presence of air.

10. METHODS OF PREPRATION:
Composition:
Gelatinsoftcapsulesare made from
i. Gelatin
ii. water
iii. Polyhydricalcohol,suchasglycerol orsorbitol - tomake themflexible.
Preservatives:
Theyusuallycontainapreservative,suchasbeta-naphthol.
Contentof a softgel capsule isa liquid,oracombinationof miscibleliquids,a
solutionof asolid(s) inaliquid(s)ora suspensionof asolid(s)inaliquid(s).
Liquidsare an essentialpartof the capsule content.Onlythose
liquidsthatare bothwatermiscible andvolatilecannotbe includedasmajor
constituentsof the capsule contentsince theycanmigrate intothe hydrophilic
gelatinshell andvolatilize fromitssurface.Water,ethyl alcohol andemulsionsfall
intothiscategory.
Types of capsule filling materials:
There are three primarytypesof innerfill materials:
1) NeatSubstance:especiallyoilyliquidse.gCodliveroil capsules
2) SolutionFills:Activedissolvedinacarrierƒ Oilssuchas soybeanoil .Anyothersolvent,whichdoesnotdegrade or
solubilize the gelatinshell,i.e.dimethyl iso-sorbide,surfactants,di-ethylene glycol mono-ethyl ether.
 Optional Ingredientsforsolutionfills:
 Water or alcohol:upto 10% w/w (if neededforsolubility).
 Glycerin:1 to 4% w/w(to retardthe migrationof the glycerinoutof the shell intothe fill).
 Polyvinyl pyrrolidone:Upto 10% w/w usedincombinationwithPEG(canincrease drugsolubility,and
alsoimprove stabilitybyinhibitingdrugrecrystallization).
3) SuspensionFills:Active dispersedinacarrier.
o Suspensionscanaccommodate about30% solidsbeforeviscosity andfillingbecome aproblem
o Suspensionscanbe heatedupto 35ºC to decrease viscosityduringthe fillingprocess
o Suspendedsolidsmustbe smallerthan80 mesh -- mill orhomogenize before fillingtopreventneedlesfrom
cloggingduringfilling
Base Adsorptionof solidsto be suspendedinsoft gelatincapsules
Base adsorptionisexpressedasthe numberof grams of liquidbase requiredtoproduce acapsulatable mixture
whenmixedwithone gramof solid(s).The base adsorptionof asolidisinfluencedbysuchfactorssuchas the
solidsparticle size andshape,itsphysicalstate (fibrous,amorphous,orcrystalline),itsdensity,itsmoisture
content,andits oleophilicorhydrophilicnature.
Large-scale manufacture Rotary capsule machine:
Thismachine hastwo, side-by-sidecylindersineachof whichhalf moldsare cut.These cylinders,like the rollers
of a mangle,rotate incontrarydirectionandas theyare mirrorimagesthe moldscome togetherpreciselyduring
rotation.Tworibbonsof gelatinare fedbetweenthe rollersand,justbefore the opposingrollersmeet,jetsof
medicamentpressthe gelatinribbonintothe molds,fillingeachhalf.The momentof pressure follows,
immediatelysealingthe twohalvestogethertoforma capsule.These
rotary machinesare capable of producingbetween25000 and 30000
capsulesanhour withan accuracy of dosage of approximately±1 percent.
Seamlessgelatincapsule:
Anothermethodof makingsoftcapsulestakesadvantage of the
phenomenonof dropformation. The essential partof the apparatus
consistsof twoconcentrictubes.Throughthe innertube flowsthe
medicamentand,throughthe surroundingoutertube,the gelatinsolution.
The medicament,therefore,issuesfromthe tube surroundedbygelatin

11. and formingaspherical drop.Thisisensuredbyallowingthe droptoformin liquidparaffininwhichthe gelatinis
insoluble.Regularinducedpulsationscause dropsof the correctsize to be formed,anda temperature of 4°C
ensuresthatthe gelatinshell israpidlycongealed.The capsulesare subsequentlydegreasedanddried.
Formulationof soft gelatincapsules
 Gelatinshell formulation:Typical softgelsare made upof gelatin,plasticizer,andmaterialsthatimpart
the desiredappearance (colorants),andsometimesflavors.
 Plasticizers:Theseare usedtomake the softgel shell elasticandpliable.Theyusuallyaccountfor20-30%.
The most commonplasticizersusedinsoftgelsisglycerol,althoughsorbitolandpropyleneglycol are
usedfrequentlyoftenin combinationwithglycerol.
 Water: The otheressential componentof the softgel shell iswater.Waterusuallyaccountsfor30-40 %
of the wetgel formulationanditspresence isimportanttoensure properprocessingduringgel
preparationandsoftgel encapsulation
 Colorants:Colorants(soluble dyes,orinsoluble pigmentsorlakes) andopacifiersare typicallyusedinthe
wetgel formulation.Colorantscanbe eithersyntheticornatural,and are usedto impartthe desiredshell
colorfor product identification.
Coating capsules:
Coatingshave beenappliedextemporaneouslytoenhance appearance andconceal taste,aswell astoprevent
release of the medicationinthe stomach(entericcoatedproducts).Capsulescanbe coatedtodelaythe release of
the active drug until itreachesa selectedportionof the gastrointestinal tract.Materialsfoundsuitable includestearic
acid,shellac,casein,cellulose acetate phthalate andnatural andsyntheticwaxes;the basisof theiruse istheiracid
insolubilitybut alkalinesolubility
Pharmaceutical applications:
Owingtotheirspecial propertiesandadvantages,softgelatincapsulesare
usedina wide varietyof industries,buttheyare usedmostwidelyinthe
pharmaceutical industry.Billionsof capsulesare made eachyearinvarious
sizesandshapes,andina varietyof colorsand colorcombinations.Their
pharmaceutical applicationsare:
1- As an oral dosage formof ethical orproprietaryproductsforhumanor
veterinaryuse.
2- As a suppositorydosage formforrectal use,orfor vaginal use.Rectal
dosage formsare becomingmore acceptable forpediatricandgeriatricuse,vaginal use isconfinedto
applicationsthatrequire the medicationtobe insertedatbedtime.
Because of the action of the sphinctermuscle,rectal use isnot
similarlylimited.
3- As a specialtypackage intube form,forhumanand veterinarysingle
dose applicationof topical ,ophthalmic,andoticpreparations,and
rectal ointments.
4- In the cosmeticindustry,these capsulesmaybe usedasa specialty
package for breathfresheners,perfumes,bathoils,suntanoils,and
variousskincreams.

12. 5- Dosage accuracy/uniformity:Precise fill volumeof liquidfillunitdeliversagreaterdegree of accuracy and
consistencyfromcapsuleto-capsule andlot-to-lot.
6- Consistentmanufacturingrequirements:More accurate compounding,blending,anddispensingof liquidfill
facilitatesmanufacturing.Liquidblendsare more homogeneous.
7- Enhancedstabilityandsecurity:The tighthermetical sealingprotectsfill fromairandenvironmental
contamination.Gelatinshellcanbe formulatedtoblockoutultravioletlight.Streamlined,onepiece designis
tamper-evident.
8- Pliable shell:softgel shell allowsforcustomshapesandsizesappropriatefororal,topical,chewable and
suppositorydelivery.
9- Portability:Encapsulatedliquiddosage formulationsbecomehighlyportable forconsumers/patients.
MICROOENCAPSULATION
Microencapsulation is a process by which solids, liquids or even gases may be enclosed in
microscopic particles by formation of thin coatings of wall material around the substances.
It is a well design drug control delivery system that can overcome some of the problems of
conventional therapy and enhance therapeutic efficacy of a drug.
Reasons for microencapsulation:
1- Isolation of core from its surroundings, as in isolating vitamins from deteriorating effects of
oxygen.
2- Retarding evaporation of a volatile core.
3- Improving the handling properties of a sticky material.
4- Isolating a reactive core from chemical attack.
5- For controlled release of drug.
6- Masking the taste or odor of the core.
7- For safe handling of the toxic materials.
8- To get targeted release of drug.
Fundamental considerations:
 Nature of the core and coating materials.
 Stability and release characteristics of the coated materials.
 The microencapsulation methods.
Core materials:
 The core material is defined as the specific material to be coated.
 The core material can be liquid or solid in nature.
 The composition of the core material can be varied( as the liquid core can include dispersed and/ or
dissolved materials)
 the solid core can be single solid substance or mixture of active constituents, stabilizers ,diluents,
excipients and release rate retardants or accelerators.

13. Coating materials:
 The selection of the coating material decides the physical and chemical properties of the resultant
microcapsules/microspheres.
 While selecting a polymer the product requirements should be taken into consideration are
stabilization, reduces volatility, release characteristics, environmental conditions etc.
Techniques to manufacture microcapsules:
1- Pan coating
2- Air-suspension coating
3- Centrifugal extrusion
4- Vibrational nozzle
5- Spray-drying
6- Matrix polymerixation
7- In-situ polyemrization
8- Ionotropic gelatio
Applications of microencapsulation:
The applications of microencapsulation re numerous.the ones mentioned below are some of them:
 Adhesives
 Anti-corrosive agents
 Carbonless copy paper
 Essential oils or flavors
 Pesticides and herbicides
 Powder perfume
 DNA protection from degradation for product tracing
 Self-heating materials such as novel plastics that can automatically repair damage.
QUALITY AND CONTROLL MANAGEMENT:
IN PROCESS TESTING:
During encapsulation process important tests are:
 The gel ribbon thickness.
 Soft seal thickness at the time of encapsulation.
 Fill matrix weight and capsule shell weight.
 Soft gel shell moisture level and soft gel hardness at the end of drying stage.
QUALITY CONTROL TESTS; Quality tests are divided into
 Physical Tests
 Chemical test
1. PHYSICAL TESTS

14.  Disintegration test.
 Weight variation test.
i. DISINTEGRATIONTEST:
Disintegration test determines whether capsule disintegrates within prescribed time when placed in liquid medium.
METHOD:
 The capules are placed in basket rack assembly,which is immersed 30 times per minute into a
thermostatically controlled fluid at 37c.
 RESULT:Capsules disintegrates completely into a soft mass having no firm core.
ii. Weight Variation TEST:
 The uniformity of dosage units may be demonstrated by weight variation for hard and soft gelatin
capsules.
METHODS:
 The gross weight of 10 intact capsules is determined individually.
 Then each capsules is cut opened and the contents are removed by wasing with suitable solvent.
 The individual shells are weighed and the net contents are calculated.
 From the results of assay,the content of active ingredients in each of capsule is determined.
2. CHEMICALTESTS: It includes:
 Dissolution test.
 Assay.
 Soft gel thickness at the time of encapsulation.
 stability testing.
 Moisture permeation test.
I. DISSSOLUTION TEST:
 The dissolution test is carried out using the dissolution apparatus official ic U.S.P.
 The capsules are placed in apparatus, that is placed in dissolution medium and rotates at specified
speed.
 The dissolution medium is held covered 1000 ml glasses and maintained at 37c at constant
temperature.
 The stirrer speed and dissolution medium is specified according to monographs.
FACTORS AFFECTINGDISSOLUTION:
 Dissolution rate of shell.
 Rate of penetration of dissolution medium.
 Rate of degradation of powder mass.
 Nature of primary drug particles.
CONTENT UNIFORMITY:
 The amount of active ingredients determined by assay ,is within the range of 85% -115% of the label claim for
9 of 10 dosage units assayed,with no unit outside the range of 70% to 125% of label claim.
II. STABILITYTESTING:

15.  Stability testing of capsules is performed to determine the intrinsic stability of active drug molecule
 And influence of environmental factors,such as temperature,humidity , light .
III. MOISTURE PERMEATION TEST:
 The degree and rate of moisture is determined by packaging the dosage unit together with a colour revealing
desiccant.
 Exposing the packaged unit to know relative humidity over a specified time, observing the desiccant pellet for
color change indicating absorption and moisture.
 Now measure the pretest weight and post test weight of pellet,amount of moisture can be determined.
ADVANTAGES OF CAPSULES:
1. IMPROVED DRUG ABSORPTION:
Improved rate and extent of absorption and reduced variability, mainly for poor water soluble drugs.
2. PATIENT COMPLAINCE ANDCONSUMER PREFERNCE:
Easy to swallow ,absence of poor taste or other sensory problem.
3. SAFETY-POTENT AND CYTOTOXIC DRUGS:
Avoids dust handling problems during manufacturing.better operator safety and environmental control.
4. OIL AND LOWMELTING POINT DRUGS:
Overcome the manufacture problems as compressed tablets.
5. PRODUCT STABILITY:
Drugs are protected against oxidative degradation by lipid vehicles and soft gel capsules shell.
6. DOSE UNIFORMITYFOR LOWDOSE DRUG:
 In soft gel dosage form, liquid flow dosage during manufacture is more precise than powder flow.
 Drug solution provide improved homogeneity over powder, granule mixtures.
7. OTHER ADVANTAGES:
 Smooth , slippery, easy swallowing nature of capsule shells made for drug make it easy to use.
 Minimum excipients required.
 It is available in different sizes and shapes.
 There is rapid drug release from capsules.
 They are easy to handle and carry.
 The shells are physiologically inert and easily digested in GIT tract.
 The shells can be opacified(with titanium oxide)or colored to give protection from light.
 As compared to tablets less adjunct is required.

16. DISAVANTAGES OF CAPSULES:
i. Capsules are not usually used for the administration of extremely soluble material for example potassium
chloride,potassium bromide or ammonium chloride because sudden release of these compounds can cause
irritation.
ii. Capsules should not be used for dilequescent materials or effeverscent materials.
iii. Special conditions for storage are required.
iv. The concentrated solutions which previous dilution require unsuitable for capsule.
v. Filling equipment is slower.
OTHER TYPES OF CAPSULES:
1) ORAL ADMINISTRATION OF CAPSULES:
• The solid dosage forms, capsules are taken by placing the dose upon tongue and swallowing it with a glassful
of water.
• The oral administration of medication is in relation to meals is important,since the biovailability and efficacy
of certain drugs may be severly affected by food.
• Dosage forms with special coating are designed to provide controlled drug release and to preserve it, capsule
should not be chewed,broken or crushed.
2) CHEWABLE SOFTGELS CAPSULES:
 It is a highly flavoured shell is chewed to relese the drug liquid fill matrix.
 The drugs may be present in both the shell and the fill matrix.
3) SUCKABLE SOFT GELS:
 It consists of a gelatin containing the flavoured medicament to be sucked and a liquid matrix or just air inside
the capsule.
4) TWIST-OFF SOFTGELS CAPSULES:
 These are designed with a tag to be twisted or snipped off, thereby allowing access to the fill material.
 This type of softgel can be very useful for unit dosing of topical medication, inhalation, or indeed for oral
dosing of a paediatric product.
5) MELTABLE SOFT GELS CAPSULE:
 It is designed for use as a “patient- friendly’ pessaries or suppositories.
COMPENDIAL REQUIREMENTS FOR CAPSULES:
Added Substances:
Substancesaddedtoofficial preparations,includingcapsules,toenhance theirstability,usefulnessor elegance orto
facilitate theirmanufacturemaybe usedonlyif they:
 Are harmlessinthe quantitiesused
 Do not exceedthe minimumamountsrequiredtoprovide theirintendedeffect
 Do not impairthe product’sbioavailability,therapeuticefficacyorsafety
 Do not interfere withrequisitecompendiaassaysortests

17. Containers for Dispensing Capsules:
The USP listsspecificationsprescribingthe type of containersuitableforthe repackagingordispensingof each
official capsule ortablet.Dependingnthe itemthe containermaybe requiredtbe light, well-closed,resistantand/or
all of these.
Inspecting, Counting, Packaging, and Storing Capsules:
INSPECTING:
Capsulesproducedona small ora large scale shouldbe uniforminappearance.Visual orelectronicinspection
shouldbe undertakentodetectanyflawsinthe integrityandappearance of the capsules.Defective capsulesshould
be rejected.Incommercial manufacture,CurrentGoodManufacturingPractice regulationsrequire thatif the number
of productionflawsisexcessive,the cause mustbe investigatedanddocumentedandstepsundertakentocorrect
the problem.
COUNTING:
In the pharmacy,
capsulesmaybe
countedmanuallyor
by automated
equipment.Specially
designedtrays,are
usedforcounting
small numbersof
soliddosage units,
as showninfig.
Fig. Abbott-Sanitary Counting Tray. A. Transferring units from stock package to tray. B.Counting
and transferring units to trough. C. Returning excess units to stock container. D. Placing the counted units in prescription
container.
Working: In usingthistray,the pharmacistpoursa supplyof capsulesfromthe bulkstore onto the cleantrayand,
usingthe spatula,countsand sweeps the dosage unitsintothe troughuntil the desirednumberisreached.Thenthe
pharmacistclosesthe troughcover,picksup the tray,
returnsthe uncounteddosage unitstothe bulk
containerbythe meansof the lipat the back of the
tray, placesthe prescriptioncontaineratthe opening
of the trough,and carefullytransfersthe capsulesinto
the container.
Withthismethod,the dosage units
remainuntouchedbythe pharmacisttopreventbatch-
to-batchcontaminationthe traymustbe wipedclean

18. aftereach use,because powder,particularlyfromuncoatedtabletsmayremain.Insome communityandhospital
pharmacies,small automatedcounting fillingmachinesmaybe used,asshowninfig.
On industrial scale, soliddosage formsare countedbylarge automatedpiecesof equipmentthatcountand transfer
the desirednumberof dosage unitsintobulkcontainers.The containersare thenmechanicallycapped,inspected
visuallyorelectronically,labeled,andinspectedonce more.Some filled containersare thenplacedinouterpackaging
cartons.Capsulesare packedinglassor inplasticcontainers,some containingpacketsof adesiccanttoprevent
absorptionof excessive moisture.
PACKAGING:
The unit-dose andstrippackagingof soliddosage forms,particularlybypharmaciesthatservice nursing
homesandhospitals,providesanitaryhandlingof the medications,easeof identificationandsecurityin
accountabilityformedications.Typicalsmall-scalestrippackagingequipmentandcommercial unit-dose packagesof
capsules.
STORAGE: Capsulesshouldbe storedintightlycappedcontainersinacool,dry place.

19. REFERENCES:
1- Ansel’s pharmaceutics
2- Remington pharmacy
3- The knowledge and practice of industrial pharmacy
4- Wikipedia