Capsules

The word “capsule” is derived from the Latin word “capsula”

meaning small box.
Definition;
Is defined as a solid unit dosage form in which one or more
medicinal and inert ingredients are enclosed within gelatin or other
polymeric shell.

Advantages
1) Capsule mask the taste and odor of unpleasant drugs and easily
administered
2) Swallowing is easy for most patient, since shell is smooth &
hydrates in mouth.
3) The shells are physiologically inert and quickly digested in GIT
4) The shells can be opacified to protect from light
5)Many problems associated with tableting like poor compaction can
be eliminated
6) Better bioavailability than tablets and faster onset of action than tablets.

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 Disadvantages
1) Hygroscopic drugs are not suitable for filling into capsules,
because they absorb water present in capsule shell makes shell very
brittle and ultimately lead to crumble into pieces.
2) The concentrated solutions which require previous dilution are
unsuitable for capsules because if administered as such lead to
irritation into stomach.
3) Since gelatin is from animal origin. Capsule made from gelatin
are susceptible to microbial contamination.
4)Deliquescent material are not suitable for filling into capsules,

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Formulation/Raw
materials of Shell
⚫ Capsule shell is manufactured with gelatin or HPC or Starch.
Gelatin is heterogeneous product derived by hydrolytic extraction of animal's
collagen of the tissues by boiling in water. it swells up in cold water, but dissolve
only in hot water.
The sources of gelatins including animal collagenous tissues like, skin, tendons,
ligaments and bones.
Advantages of gelatin
Soluble in biological fluids at body temperature
Good film forming material- Producing a strong flexible film
Walls of gelatin capsules are homogeneous and robust, can readily withstand
mechanical stress of filling and packaging operations
TYPES OF GELATIN
Type A
Type B
Advance Type B
⚫

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Gelatin is heterogeneous product derived by hydrolytic extraction of
animal's collagen of the tissues by boiling in water. it swells up in cold
water, but dissolve only in hot water.
The sources of gelatins including animal collagenous tissues like, skin,
tendons, ligaments and bones.
Advantages of gelatin
Soluble in biological fluids at body temperature
Good film forming material- Producing a strong flexible film
Walls of gelatin capsules are homogeneous and robust, can readily
withstand mechanical stress of filling and packaging operations
TYPES OF GELATIN
Type A
Type B
Advance Type B

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Formulation of Shell/ Raw
materials
⚫ Type B
⚫ Type A ⚫ Obtained using alkaline
⚫ Obtained by acid treatment of treatment of demineralised
animal (pig) skin (HCl, bones (Immersion in calcium
H2SO4, H2SO3), pH1-3 for hydroxide slurry for 1-3
approximately 1 day months)
⚫ Isoelectric point pH 7-9 ⚫ Isoelectric point pH 4.7-5.3
⚫ Requires more time for
⚫ Requires less time for
manufacturing.
manufacturing.

Advance type B is obtained by first acidic and then basic hydrolysis

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 Preparation Of Gelatin

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Alternative material for HGC
⚫ Hydrolysate (Capill), Hydroxypropyl methyl cellulose, chitosan,
HPC or Starch
⚫ HPMC best alternative- overcome the problem of brittleness, when
exposed to dry conditions.
⚫ Colorants
⚫ Water soluble dyes: Azo dyes and non azo dyes(most commonly
used)- erythrosine, indigo carmine, quinoline yellow
⚫ Insoluble pigments: black, red and yellow iron oxide

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Formulation of Shell/ Raw
materials
⚫ Opacifying material-
⚫ Capsules are made opaque to protect from light. Example: Titanium dioxide.
⚫ Plasticizers
⚫ Improve the flexibility of shell eg. Glycerin, sorbitol, PEG or combinations
thereof
soft gelatin capsule the plasticizer and gelatin ratio is
0.8 : 1
In hard gelatin capsule the plasticizer and gelatin ratio is
0.4 : 1
Preservatives
⚫ Moisture content of gelatin is 16%, bacterial growth may occur, therefore
addition of preservatives like Parabens, sorbic acid, benzoic and propanoic acid
etc is needed.
Flavor & sweetener

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Capsule Size
Empty capsules ranging in size from 000 the largest(Veterinary) to 5
the smallest (human application). Generally, hard gelatin capsule are
used to encapsulate between 65 mg to 1 gram.

SIZE AND CAPACITIES

SIZE: 000 00 0 1 2 3 4 5
Capacity
in ml: 1.37 0.91 0.75 0.55 0.4 0.3 0.25 0.15
Capacity
in mg: 950 650450 300 250 200 150 100
Height mm 26.14 23.3 21.7 19.4 18 15.9 14.3 11.1

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II. SELECTION OF
CAPSULE SIZE

Size of hard gelatine capsule is selected depending on the

quantity of material to be filled in the capsule

The density and compressibility of a powder can also affect the selection of
capsule size.
Degree of pressure used in filling the capsules is also needed to be considered.

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To determine the size of capsule to be used the following relationship is used:

Capsule capacity (mg) =

Tapped Density of Formulation X Capsule Volume

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Hard gelatin capsule shell
manufacturing
Steps involved in making empty gelatin
capsules…

1. Dipping
2. Spinning
3. Drying
4. Stripping
5. Joining
6. Polishing

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Hard gelatin capsule shell
manufacturing

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Hard gelatin capsule shell
manufacturing
Dipping :
Pairs of the stainless steel pins are dipped into the melted gelatin
mixture present in temperature controlled reservoir (about 450C)
Spinning :
The pins are rotated to distribute the gelatin over the pins uniformly
Drying :
The gelatin is dried by a blast of cool air to form a hard shells.
The water from capsule shells is removed by moving pins through air
drying sections.
Stripping :
The shells are removed from pins by bronze jaw.

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Hard gelatin capsule Shell
manufacturing
⚫ Trimming The stripped cap and body portions are trimmed to the
required length by stationary knives.
⚫ Joining
After trimming to the right length, the cap and body portion are joined

Polishing
Pan Polishing : Acela-cota pan is used to remove the dust and polish.
Cloth Dusting : Capsule are rubbed with cloth.
Brushing : Capsule are feed under soft rotating brush.

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Defects in hard capsule shell
⚫ HGC is having majoritily two kinds of defects
⚫ Visual quality defects and printing defects

⚫ Visual quality defects are classified into Critical defect, Major

defect and Minor defect

CRITICAL DEFECTS:
Pin holes- Irregular opening in the cap
Cracked capsule- Cap or body with slits
Mashed capsules- Mechanically damaged capsules with many slits,
Uncut body/cap- An untrimmed cap or body

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Defects
⚫Major defects
in hard capsule shell
⚫ Double cap- Capsule with an additional cap covering the body
⚫ Dents- The depression formed in the cap or body
⚫ Loose body, cap
⚫ Long or short capsule- Axial length is long or short
⚫ Minor defects
⚫ Foreign material- Foreign matter on the surface(oil, dust)
⚫ Color spots- spot of different colour gelatin
⚫ Bubbles- An air bubble in the cap or body wall which has a
diameter greater than 0.4 mm
⚫ Foreign capsules- Wrong size and colored capsule in the packet
⚫ Heavy end- End of capsule is thick
Printing defects- Missing print, ink spot, light print, dark print, Incomplete
letters.

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Finishing of capsules
It involve sealing and polishing of capsule. Polishing is discussed in the
manufacturing of gelatin shell

Madhuri Gaikwad, Assist

Prof, AIKTC, new Panvel 19
Storage/ humidity control
Humidity andin
is needed as
capsule
temperature control

Moisture absorption causes

distortion. `
⚫ Storage/ humidity control Moisture loss from capsule result in
in capsule brittle and crumble capsule.
manufacturing- Capsules
Desicant bags (Silica gel, clay and
should be stored between
20° C to 25° C (59° F to 77° activated charcoal), should be placed in
capsule shell packet to avoid the moisture
F) temperature and within effect.
40% and 60% relative
humidity. Keep capsule bags ⚫ Humidity control in capsule
sealed when not in use.
Keep capsules away from manufacturing and filling
any direct source of heat & area:
light. Avoid sudden transfer ⚫ Empty capsule shell usually contain
of capsules from high the moisture between 12-16%.
temperature to low Capsule filling is carried out at the
temperature zone. temperature 20-250 C and relative
humidity 30-45% (Maximum 40%
in operation area and 20-30% in
drying area)
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 Difference

Soft gelatin capsule Hard gelatin capsule

⚫ Less plasticized than SGC

⚫ Gelatin film contains more plasticizer
⚫ Capsule shell is prefabricated and supplied
⚫ Encapsulation and filling take place empty. Filling of material is different operation
simultaneously
⚫ Two parts (Cap, body), which can be opened
⚫ Hermetically sealed and can’t open without and joined again
distroying ⚫ Mostly formulated in cylindrical shape
⚫ Available in different shapes round, oval,
oblong
⚫ 65 mg- 1 gm
⚫ Content 0.1-30 mL
⚫ High weight variation due to poor powder flow
⚫ Drug dissolved in vehicle and filled and mixing
volumetrically. Less chances of weight variation
⚫ High moisture uptake tendancy ⚫ Low moisture uptake tendency
⚫ Drug is in liquid form hence more ⚫ Encapsulated material has to disintegrate or
bioavailability than hgc dissolve before absorption, less bioavailability
than SGC
⚫ Filling material includes powders, granules,
⚫ Oily solution/suspension or emulsion is filled beads and pellets
⚫ Method of preparation include rotary die ⚫ Manufactured by dipping process but nowadays
process, plate process, and accogel the process is fully automated
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Types of fills and excipients for HGC/
formulation or filling material for HGC
⚫ Types of fills in capsule includes
⚫ Powder, granules,pellets, liquids, paste, tablet, and small capsule ,

⚫ Pellets: These are multiple-units of more regular shape than granules. each unit of pellet may
contain various substances with different release characteristics. In this way,
incompatibilities and interaction between the different drug substances in combination
products can be prevented. These are more spherical than granules.
⚫
⚫ Liquids: Gelatin capsules are unsuitable for the encapsulation of aqueous liquids, because
water softens the gelatin to produce distortion of the capsules.
However, some liquids such as fixed or volatile oils that do not interfere with the stability of
the gelatin shells may be placed in gelatin capsules which then may be sealed to ensure the
retention of the liquid. Liquid that dissolve gelatin (formaldehyde) are often absorbed
onto inert carrier to form dry powder suitable for capsule filling.

⚫ Semisolid Paste: Used for potent drugs to improve uniformity of filling. Used for safely
handling toxic drugs.

⚫ Capsule within capsule: If one ingredient must be separated from others in the formulation, a
small capsule, such as a No. 5, may be filled with one drug and placed into a larger capsule with
other drug.
⚫
⚫ Tablets within capsule: Small tablets are filled into capsules to produce special release forms or to
separate incompatible ingredients.

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⚫
⚫ Excipients for HGC/ formulation or filling material
⚫ Active ingredients
Drug
⚫ Excipients
⚫ Diluent: when quantity of medicament is small. To bring the medicament
up to desired bulk diluents are added eg. Lactose, mannitol, sorbitol and
starch
⚫ Adsorbent: When medicaments are physically incompatible with each other
(eg. Eutetic or hygroscopic substances) adsorbents are needed. In such
cases absorbents like oxides and carbonates of magnesium and calcium
and kaolin are added to powdered drug
⚫
⚫ Disintegrant: To assist the breakup and distribution of capsule content in
stomach disintegrants are added. eg pregelatinised starch, crosscarmellose ,
SSG
⚫ Glidants: To ensure a regular flow of powder into automatic capsule filling
machine glidants are mixed with medicaments
Eg talc, metallic stearate, stearic acid and talc
They should not exceed more than 2%

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⚫ Antidusting compound:
During filling of capsules by an automatic filling machine lot of dust comes out of
machine. This cause serious health hazard to machine operator specially from
potent drugs. Antidusting compounds like edible oil are added to avoid this.
⚫ Wetting agent
These are added if the drug is water insoluble. Addition wetting agents, as sodium
lauryl sulfate, in capsule facilitate the wetting of the drug substance by
gastrointestinal fluids to enhance dissolution.

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Difficulties in filling of capsules
1. Deliquescent or Hygroscopic powders – a gelatin capsule contain water which is
extracted or taken up by a hygroscopic drug in dry & hot environment of summer
and renders the capsule very brittle which leads to cracking of the capsule. In winter
and monsoon as the humidity is high hygroscopic material will absorb water,
affecting the integrity of shell. The addition of an adsorbent like magnesium
carbonate, heavy magnesium oxide or light magnesium oxide overcomes this
difficulty provided the capsules are packed in tightly closed glass capsule vials.
2. Eutectic mixtures – certain substances when mixed together tend to liquefy and
form a pasty mass due to the formation of a mixture which has a lower melting point
than room temperature. For filling these types of substances each troublesome
ingredient is mixed with an adsorbent separately then mixed together and filled in
capsules. The adsorbents used are magnesium oxide and kaolin.
3. Filling of potent drugs – When the quantity of the drug to be filled in capsules is
very small then inert substance or a diluent is added so as to increase the bulk of the
powder. Uneven distribution of drug may occur while mixing potent drug with large
quality of diluent. Geometric mixing process should be used to avoid the problem.
4. High pH or low pH drug: pH should be 2.5-7.5. Use salt form or adjust pH
5. Incompatible drug: Use small cap or tab
6. Iron sensitive drug: Avoid filling or use large quantity of diluent.

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Hard gelatin capsule filling machines
⚫ Classification
⚫ Powder filling machine (dosator)
Formatic, macofar, perry accofil
⚫ Pellet filling (volumetric/augur)
Rotofil
⚫ Powder, pellet and granule filling (volumetric/augur)
Eli Lilly, park devis, MG2, (dosator) Osaka (Not for pellet)
⚫ Powder, pellets, granules, liquids and tablet filling machines
Hofflinger and Karg (tamping finger), Zanasi (small capsules also)
(dosator)
⚫ Liquids filling machines (tamping finger)
Elanco, Robert Boch GmbH
Other important machines
⚫ Capsule weight controller equipment:
Rotoweight, vericap
⚫ Capsule imprinting machine:
Ackley imprinter, Markem
⚫ Machine which removes faulty capsules:
Rotosort
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Filling of hard capsule shell
⚫ Punch method/manual filling
⚫ Hand operated capsule filling machine
⚫ Automatic operated capsule filling machines

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Filling of hard capsule shell
⚫ Punch method/manual filling
⚫ Used for filling a small number of capsules in the pharmacy, at the prescription
counter.
⚫ The ingredients are triturated to the same particle size and then mixed by geometric
dilution.
⚫ The powder is placed on a powder paper or ointment slab.
⚫ The body of the capsule is held vertically and the open end is filled with powder and
repeatedly pushed or "punched“ until the capsule is filled;
⚫ The cap is then replaced to close the capsule. Each filled capsule is weighed using an
empty capsule as a counter weight.
⚫ Powder is added or removed until the correct weight has been placed in the capsule.
⚫ The filled capsule is tapped so that no air spaces are visible within the contents.

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Filling of hard capsule shell
⚫ Hand operated capsule machines/ Bench scale filling
⚫ Pharmacists that prepare capsules on a regular or extensive basis may use hand-operated capsule machines.

⚫ These machines are available in capacities of 24, 96, 100, and 144 capsules.

⚫ First, the plates are adjusted to hold the capsule bodies in place while the caps are removed all at one time.

⚫ The caps remain in place in the top of the machine for later use. Then the plates are adjusted again so that the

capsule bodies will "drop" into place so that the tops are flush with the working surface of the plate.

⚫ The formulation powder is poured onto the plate and special spreaders are used to fill the individual capsules.

⚫ The combs (pins) are used to tamp (compress) and pack the powder into the capsules.

⚫ All of the caps are then returned to the capsule bodies, and the closed capsules are removed from the machine.

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Automatic operated capsule filling
machines

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Automatic operated capsule filling
machines
Industrial –scale Filling

Dependent Independent
dosing system dosing system

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Automatic operated capsule filling
machines
⚫ Dependent dosing system
Dosing system that use capsule body directly to measure the powder
is called dependent system. Uniformity of fill weight can only
achieved if the capsule is completely filled.
Ex.: auger or screw or volumetric system
Independent dosing system
The powder is measured independently of the body in a special
measuring device. Weight uniformity is not depend on filling body
completely
⚫ Dosator
⚫ Tamping finger and dosing disc

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Automatic operated capsule filling
machines
⚫ Dependent dosing system
⚫ Auger (based on volume)
⚫ Empty capsules are held into a pair of ring holders, the cap retained in one
half and the bodies in other. The body holder is placed on a variable speed
revolving turntable; the powder hopper is pulled over the top of this plate.
In the hopper, a revolving auger forces powder down into the capsule
bodies. The weight of powder is
dependent mainly upon the time the body is underneath the hopper during
revolution of the plate holder.

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Automatic operated capsule filling
machines
⚫ Independent dosing system
⚫ In this pistons or tamping pins lightly compress the individual doses of the
powders into plugs( also called as slugs) and eject the plugs into empty
capsule bodies
⚫ Dosators
⚫ Consist of dosing tube. The tube is lowered , open end first get into bed of
powder, which form plug. This can be further consolidated by applying
compression force with piston. The assembly is then raised from powder
bed and positioned over capsule body. The piston is lowered ejecting the
powder plug into the capsule body.
⚫ Eg of machines- Zanasi, Macophar, MG2

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35
Automatic operated capsule filling
machines
⚫ Independent dosing system
⚫ Tamping finger and dosing disc

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Automatic operated capsule filling
machines
⚫ Hopper consist of dosing disc at the bottom. The disc has series of
sets of accurately drilled holes in which powder plugs are formed by
sets of tamping fingers.
⚫ Tamping fingers lowered into the bed of powder and compress the
material in hole, forming plug. At the last position finger pushes the
plug through the disc into capsule body.

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Soft gelatin capsule
o Soft Gelatin capsules are one piece, hermetically sealed, soft gelatin shells. The
shells are softened by using appropriate ratio of gelatin and plasticizer. They are
called as one piece capsule. They are used to deliver lipophilic drug (cod liver
oil, vitamin A and vitamin D) and liquids ( Solution, suspension, emulsion).
They are available in variety of shapes
Spherical 0.5-5 mL, ovoid 0.05-7 mL, cylindrical- 0.15-25 mL
Advantages:
• Improve bioavailability (particularly for water insoluble drug)
• Easy to swallow
• Convinient for administration of liquid drug
• Avoid dust handling problem during manufacture
• Safe as they are tamper resistant and
• Drus is protected from environmental degradation
• Homogenity in dose
Soft gelatin is mainly composed of gelatin, plasticizers, preservative, colouring and
opacifying agents, flavoring agents and sugars.

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Soft gelatin capsule
⚫ Disadvantage
⚫ 1. Requires special manufacturing equipment
⚫ 2. Limited choices of excipients/carriers compatible with the gelatin
⚫

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Shape of SGC

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 Formulation of filling material SGC
⚫Materials not incorporated in SGC
⚫ Water miscible, volatile liquids can not be included in capsules as they
can migrate into hydrophilic gelatin shell and evaporate from surface.
Similarly glycerin and propylene glycol cannot be dispensed because they
causes softening of shell.
⚫ All the preparation should have pH range 2.5-7.5.Preparation is more
acidic causes hydrolysis and leakage of gelatin shell and alkaline
preparation can tan gelatin and affect the solubility.
⚫
⚫ Types of fill in SGC is as follows:
⚫ Neat substance/especially oily liquids: Cod liver oil
⚫ Solutions: (API dissolved in lipophilic liquids Soyabean oil and miglyol
or other solvents: dimethyl isosorbide, diethylene glycol, monoethyl
ether

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Formulation of filling material SGC
⚫ Suspensions: suspension consisting of 30% solids can be
incorporated. Suspensions can be heated up to 35ºC to decrease
viscosity during the filling process.
⚫ Suspended solids must be smaller than 80 mesh, mill or homogenize
before filling to prevent needles from clogging during filling.
⚫ Solids that are not sufficiently soluble in liquids or in combination
of liquids are capsulated as suspensions.

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Specifications for soft gelatin shell
⚫ Bloom strength or gel strength
⚫ Measurement of cohesive strength of crosslinking between gelatin
molecules is called bloom strength and is propotional to mol wt of
gelati. 150-250g is normal range of bloom strength. Higher the gel
strength more will be physical stability.
⚫ Viscosity: 25-45 millipoise is the optimum viscosity required to
produce non-tacky and non-brittle shells. Low viscosity (25-32
millipoise) and higher bloom strength (180-250) gelatin is used for
hygroscopic material
⚫ Iron content: iron is present as impurity in gelatin. Total iron content
should not be more than 15 ppm, because above this concentration
iron can react with aromatic compound.

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 Specifications for soft gelatin shell
⚫ Base absorption
⚫ It determine minimum capsule size for encapsulation. Higher the
base absorption higher will be size of capsule.
⚫ No of grams of liquid base required to produce a capsulable
mixture of 1 gm solid substance is called as base absorption.

BA=Wt. of liquid base/wt of solid (1g)

⚫Minim per gram factor

⚫ It is volume in minim occupied by mixture of 1g of solid (S) and
weight of liquid base (BA) required to produce capsulable
mixture.

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Soft gelatin capsule fill machines
⚫ Liquid filling
⚫ 1) Plate process
⚫ 2) Scherer Rotary die process
⚫ 3) Reciprocating die process
⚫ Solid filling
⚫ 4) Accogel process

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Soft gelatin capsule fill
machines-Rotary die process
•Preparation of gelatin mass:-
• The gelatin is weighed and mixed with accurately measured
components (plasticizers etc) in a suitable equipment such as pony
mixer.
• The resultant fluffy mass is transferred to melting tanks and
melted under vacuum at 930C. The mixing process requires about 25
min for 270 kg of mass, and the melting process require about 3 hours.
• The sample of the resulting fluid mass is visually compared
with a color standard, and additional colorants are blended into the
mass if adjustment are required.
• The mass is then maintained at a temperature of 57-600C before
and during the capsulation process.

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Soft gelatin capsule fill machines-Rotary
die process
• Prepration of fill materials:- The solids (drugs etc) are mixed
with the liquid base, and the mixture is passed through a
homogenizing equipment such as colloidal mill, so that the solids
are thoroughly wetted with the liquid carrier and a smooth
homogeneous mixture is obtained.
•Deareation of the liquid mixture:- After homogenization all
liquid mixture are subjected to deaeration. It is required to
achieve uniform capsule fill weight, it also prevents loss of
potency through oxidation. When small amount of volatile
ingredients are included in a formulation , they should be added
after deaeration.
• The deaeration equipment expose the liquid mixture
continuously to a vacuum. After deaeration the mixture is ready
for encapsulation.

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 •In – process quality control of the fill mixture:-
Soon after deaeration a sample of the mixture is sent
to the quality control department for various tests such as
assay, specific gravity, moisture content, air entrapment and
tests for homogeneity of the suspension

•Encapsulation:- (rotary die process)

•

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Soft gelatin capsule fill machines-Rotary
die process
•Drying :-
Immediately after manufacturing the capsule are washed in
naphtha to remove the mineral oil lubricant. The washed capsule are
dried in an infrared dryer and then spread on trays for final drying
under conditions of 20-30% relative humidity and 21-240C temperature.
All the processing area, except gelatin preparation department,
should be air-conditioned (40%RH at 20-220C) to assure proper
conditioning of the gelatin films

•In-process checking:-
During manufacturing capsules are taken at intervals and
checked for seal thickness(microscopy) and fill weights.
For the determination of the fill weight each capsule is
weighed and the contents removed by cutting open the capsule. The
shell is then washed with petroleum ether, and the empty shell is
reweighed.

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Evaluation of empty shell
⚫ 1) Identification test of gelatin
⚫ Boil 1 capsule in 25 mL of water, allow to cool and centrifuge. To 5
mL supernatent add 1 mL tannic acid- precipitate is produced.
⚫ 2) Microbial limit- Crush one capsule, observe it under microscope
for microbial count
⚫ Limit- NMT 1000 microbes/ gm of capsule. It should be free from
E.Coli and salmonella
⚫ 3) Loss on drying- 12-16% determined by drying 1 gm shell in
oven for 4hrs to constant weight
⚫ 5) Length of capsule and body- Vernier caliper
⚫ 6) Appearance- Cracks,leak
⚫ 7) Depth/capsity

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Capsule evaluation test
⚫ Official
⚫ Dissolution
⚫ Disintegration
⚫ Weight variation
⚫ Content uniformity
⚫ Content of active ingredients
⚫ Non- official
⚫ Evaluation of shape, size, color,thickness, leaking

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Capsule evaluation test
⚫ Disintegration

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Capsule evaluation test
⚫ Disintegration
⚫ Take 6 capsules, place in 6 tubes of disintegration apparatus. If the
capsule float a disc may be added. The capsules must disintegrate
and all the particles must pass through the 10# screen in the time
specified. All uncoated capsules should disintegrate in 0-30 min in
water at 370C±2 0C. Enteric coated capsule should not show any
evidence of disintegration after 2 hrs in simulated gastric fluid or
water or 0.1N HCL but should get disintegrated within 1 hr in 6.8
phosphate buffer. If it fails repeat on additional 12 capsules and 16
should pass the test.
⚫ This test is not applicable for sustained release capsules and those
capsules for which the dissolution test included in monograph.

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Capsule evaluation test
⚫ Dissolution
⚫ USP types of dissolution appratus
⚫ Apparatus 1 - Basket (37º)
⚫ Apparatus 2 - Paddle (37º)
⚫ Apparatus 3 - Reciprocating Cylinder (37º)
⚫ Apparatus 4 – Flow-Through Cell (37º)
⚫ Apparatus 5 – Paddle over Disk (32º), Transdermal Delivery System,
use paddle and vessel from Apparatus 2 with a stainless steel disk
assembly to hold the transdermal on the bottom of vessel.
⚫ Apparatus 6, Cylinder (32º), Transdermal Delivery System, use
Apparatus 1 except replace the basket shaft with a stainless steel cylinder
element.
⚫ Apparatus 7, Reciprocating Holder, for transdermal delivery systems
and also a variety of dosage forms

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Capsule evaluation test
⚫ Apparatus 1 (Basket) or Apparatus 2 (Paddle

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Capsule evaluation test
⚫ Dissolution: - The dissolution test is carried out using the dissolution apparatus
official in both the U.S.P. and IP. - The capsule is placed in a basket formed
from 22-mesh stainless steel fabric. - A stirrer shaft is attached to the basket, and
the basket is immersed in the dissolution medium and caused to rotate at a
specified speed. - The dissolution medium is held in a covered 1000 ml glass
vessel and maintained at 37°C ± 0.5°C by means of a suitable constant
temperature water bath. - The stirrer speed and type of dissolution medium are
specified in the individual monograph

⚫ Weight variation test

This test is to be done on 20 capsules.
Method:
1- Weigh an intact capsule.
2- Open the capsule without losing any part of the shell and remove the contents as
completely as possible.
3- Weigh the shell.
4- The weight of the contents is the difference between the weighing.
5- Repeat the procedure with a further 19 capsules selected at random.
6- Determine the average weight

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Capsule evaluation test
Limit: Not more than two of the individual weights deviate from the average
weight by more than the percentage deviation shown in the table below, and none
deviates by more than twice that percentage.
Average weight capsule Percentage deviation
Less than 300 mg 10
300mg or more 7.5
This test is not applicable for capsules which consist of less than 10% or 10 mg of
drug, for those capsules content uniformity is applicable.

⚫ Content uniformity
30 capsules are selected and 10 of these are assayed individually. - At least 9 of
these contain 85 – 115 % of drug and none contain below 75 – 125% of drug. - If 1
to 3 of them fall outside of 85 – 115% limits, the remaining 20 capsules are
individually assayed and not more than three may fall outside of 85-115% range
but within 75-125% limit..
This test is not applicable to multivitamin and trace element capsules. This test is
applicable to potent drug capsule containing 10 mg or 10% of active ingredient.

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Capsule evaluation test
⚫ Content of active ingredient:
⚫ Take 20 capsules or other number indicated in monograph, Mix the
content. If 20 capsules can not be obtained a smaller number which
must not be less than 5 may be used- but to allow for sampling
errors the tolerance are widened. Determine the amount of active
ingredient. Result should lie within the range for the active
ingredient stated in monograph (90-110%)

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Packaging of tablet and capsule

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