• Definition: 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.
• Capsules are usually intended to be administered
orally by swallowing them whole.
• Occasionally, capsules may be administered
rectally or vaginally.
Advantages
Neat and elegant in appearance.
Tasteless shell to mask the unpleasant taste/odor of the drug.
The contents may be removed from the gelatin shell and employed as a pre measured medicinal
powder, the capsule shell being use to contain a dose of the medicinal substance.
Commonly embossed or imprinted on their surface the manufacturer’s name and product code
readily identified.
The ready solubility of gelatin at gastric pH provides rapid release of medication in the stomach.
Packaged and shipped by manufacturers at lower cost less breakage than liquid forms.
More stable and longer shelf life.
Disadvantages
Capsules are not suitable for liquids that dissolve gelatin, such as aqueous or
hydro alcoholic solutions.
The concentrated solutions which require previous dilution are unsuitable for
capsules because if administered as such lead to irritation into stomach.
Not useful for efflorescent or deliquescent materials. Efflorescent cause
capsules to soften & Deliquescent may dry the capsule shell to brittleness.
Various Material used in capsule shell mfg.
Constituents Examples Function
Gelatin Type A, Type B
Plasticizers Glycerine USP, Imparts softness,
glycerol (85% & 98%) Elasticity & hardness
Preservatives Methyl paraben, Retard growth of
Sorbic acid (0.2%) microorganisms
Solvents Oils Elegance
Opacifying agents Tio2(0.2-1.2%) Minimize transparency
Colours Veg. colours,FD&C Gives pleasant appearance to
D&C water soluble dyes, the shells.
certified lakes
Flavours Ethyl vanillin(0.1-2%) Good flavour
Sugars Sucrose( up to 5%) Sweet taste
Acids Fumaric acid(up to 1%) Lessen aldehydic tanning of
gelatin
Thickening agents Methyl cellulose Adjust viscosity of gelatin
Water
Manufacturing of gelatin
GELATIN
Gelatin is heterogeneous product derived by hydrolytic
extraction of animal's collagen. The sources of gelatins
including animal bones, hide portions and frozen pork skin.
TYPES OF GELATIN
Type A
Type B
Types of Gelatin
TYPE A - Derived from acid treated precursor that exhibits an
iso electric point at pH-9. It is manufactured mainly from
pork skin.
TYPE B - Derived from alkali treated precursor that exhibits
an iso electric point at pH-4.7. It is manufactured mainly
from animal bones.
Manufacturing of Hard gelatin capsule
shell
Steps involved in making empty gelatin capsules…
• Dipping
• Spinning
• Drying
• Stripping
• Trimming
• Joining
• Polishing
Manufacturing of Hard gelatin capsule
shell
• Once raw materials have been received and released by Quality Control, the gelatin
and hot demineralized water are mixed under vacuum in Stainless Steel Gelatin
Melting System.
• From receiving tanks, the gelatin solution is transferred to stainless steel feed tanks.
• Dyes, opacifants, and any needed water are added to the gelatin in the feed tanks to
complete the gelatin preparation procedure.
• From the feed tank, the gelatin is gravity fed to Dipper section.
Manufacturing of Hard gelatin capsule
shell
Dipping : Pairs of the stainless steel pins are dipped into the dipping solution to
simultaneously form the caps and bodies for 12sec. The dipping solution is
maintained at a temperature of about 50º C in a heated, jacketed dipping pan & pins
are at 22ºc.
Spinning : The pins are rotated to distribute the gelatin over the pins uniformly and to
avoid the formation of a bead at the capsule ends it is rotated 2½ times by moving
upward.
Drying : The gelatin is dried by a blast of cool air to form a hard shells. The pins are
moved through a series of air drying kilns, Here gently moving air which is
precisely controlled for volume, temperature, and humidity, removes the exact
amount of moisture from the capsule halves.
Manufacturing of Hard gelatin capsule
shell
Stripping : A series of bronze jaws strip the cap and body portions of the
capsules from the pins.
Trimming and joining: The stripped cap and body portions are trimmed to
the required length by stationary knives. The cap and body lengths are
precisely trimmed to a ±0.15 mm tolerance.
After trimming to the right length, the cap and body portion are joined.
• Finished capsules are pushed onto a conveyer belt which carries them out
to a container.
• Capsule quality is monitored throughout the production process including
size, moisture content, single wall thickness, and color.
• Capsules are sorted and visually inspected on specially designed
Inspection Stations.
• Perfect capsules are imprinted with the client logo on high-speed
Defects in hard gelatin capsule shell
Quality Control of Gelatin
• Microbial limits:
• Total bacterial count should not exceed more than 1000 cfu
and test for Salmonella and E. coli species are negative.
• Identification test
• Dissolve 1 gm of gelatin in 100 ml hot water. To this
solution add 20 ml of mixture 0.2M potassium
dichromate and 3N HCl (4:1). Yellow ppt is formed.
• Residue after ignition should not me more
than 2 %.
Bloom strength/ Gel strength
• It is a measure of cohesive strength of the cross linking
that occurs between gelatin molecules.
• Bloom strength is determined by measuring the weight
in grams required to plastic plunger of 0.5 inches in
diameter, 4 mm deep into 6.66 % gelatin gel which is
kept at 10oC for 17 hours.
• Bloom strength ranges from 150 to 250 gm.
Viscosity
• Viscosity of gelatin is measured on 6% concentration
of gelatin in water at 60 oC.
• The viscosity of gelatin can range from 25 to 45
milipoise.
• Iron content:
– Gelatin used in manufacturing of soft gel capsule
should not contain 15 ppm of iron.
Evaluation of Empty Hard Gelatin
Capsule shell
• Odor
– Keep 100 capsule shells in a well-closed bottle for
24 hrs at a temperature b/w 30-40C. The
shell does not develop any forcing odor.
• Identification Test for capsules: -
– Boil one capsule shell with 25ml H2O,
allow cooling & centrifuging. To 5ml of
supernatant liquid add 1ml of tannic acid solution;
a precipitate is produced in each case.
Evaluation of Empty Hard Gelatin
Capsule shell
• Loss on Drying: -
– This test is done to check the moisture loosing
limit of capsule shell when kept in extreme
conditions.
– Procedure:-
– Between 12 %& 15 %, determined on 1g of
capsule shells by drying in an oven for 4 hrs or to
constant weight.
• Microbial Limit:-
Formulation aspects of hard gelatin
capsules
Capsule filling
• Filling of capsule by a powder is of two types
– Dependant type
• Powder is directly transferred from hopper to capsule body
and flow of powder is aided by auger or by vibrating plate
– Independent type
• In this type the required amount of powder is compressed to
form a plug in a dosator (dosing tube) and then this plug is
transferred in capsule
Volumetric Capsule filling principal
Volumetric/ Auger Capsule filling
• The powder or granules are in present in
hopper.
• Inside the hopper rotating augur along with
stirrer is present.
• Powder is flown continuously out of the
hopper with help of rotating auger.
• Below the hopper capsule body is present in
rotating turn table.
Volumetric/ Auger Capsule filling
• During rotation capsule will pass underneath
the hopper.
• Capsule body will remain underneath the
hopper for particular period of time during
which it will be filled with powder by auger
rotation.
• After filling of powder in capsule body it is
attached with cap and sealed.
Dosator principle of capsule filling
• A dosator type capsule filling machine has two
main sections – pin part and body section.
• With these, it obtains small doses of powder
from the bulk container and transfers to the
capsules.
• Stage 1
• Switching on the encapsulator machine will force the
dosator into the powder bed. This forces the powder
to fill the cavity at the tip of dosator.
• Normally the size of the cavity will depend on the level
of the dosator plunger (section in color red).
Remember, the arrows indicate how the dosator
components move.
• Stage 2
• The powder fills the cavity
and the plunger compacts it
within the dosator. This locks
the powder in the dosator
cavity.
• Stage 3
• The dosator retracts from the
powder bed carrying with it the
powder in the cavity.
• Stage 4
• At this point, the tip of the filled
dosator should be free from excess
powder. A process referred to as
“doctoring”.
• That is, cutting off the excess powder
that hangs at the tip of dosator.
• Stage 5
• Dosator can now eject the
powder in the capsules.
Tamping type
Capsule Filling Machines
(Encapsulators)
• Encapsulators, also called capsule fillers, capsule filling machines or
encapsulation machines are mechanical devices commonly used for
industrial and pharmaceutical purposes.
• These machines are used to fill empty soft or hard gelatin capsules of
various sizes with powders, granules, semi-solids or liquids substances
containing active pharmaceutical ingredients or a mixture of active drug
substances and excipients.
• This process of filling empty capsules with substances is termed
encapsulation
Operating principles of a capsule
filling machine
• Capsule filling machines should all have the following
operating principles in common.
Rectification (orientation of the bad gelatin capsules).
Separation of capsule caps from bodies.
Dosing of fill material/formulation (filling the bodies).
Rejoining of caps and bodies
Ejection of filled capsules.
Encapsulators used in encapsulation of hard gelatin
capsule can be classified or said to be of three types.
1. Manual /hand operated capsule filling machine.
2. Semi-Automatic capsule filling machine.
3. Automatic capsule filling machine.
Manual /hand operated
encapsulators
• These type of encapsulators consists of
• A bed of about 200-300 holes
• A loading tray with about 200-300 holes.
• A powder tray.
• A pin plate with about 200-300 pins
• A sealing plate with a rubber cap.
• A lever
• A cam handle with loading tray of about 250 holes on the average,
• A hand operated capsule filling machine is capable of producing about 6250
capsules per hour. This machine is used by small scale manufacturers and hospitals
for extempore preparations.
Base Adsorption
• The choice of suspension medium are directed toward producing the smallest size capsule .
• In the formulation of suspensions for soft gelatin encapsulation, certain basic information
must be developed to determine the minimum capsule size.
• Laboratory tool for this purpose is:
• Base adsorption (of solids to be suspended): is expressed as number of
grams of liquid base (insert liquid or vehicle) or minimum quantity of base
required to produce a capsulatable mixture when mixed with one gram of
solid(s).
The base adsorption of solid is influenced by :
The solid particle size and shape
Its physical state ( fibrous, amorphous or crystalline)
Its density, moisture content, oleophilic or hydrophilic nature.
Base Adsorption
• In the determination of base adsorption, the solid(s) must be completely wetted by the
liquid base. For glycol and nonionic type base, the addition of a wetting agent is
seldom required, but for vegetable bases, complete wetting of the solid s is not
achieved without an additive. Soy lecithin. at a concentration 2to3% by weight of the
oil, serves excellent for this purpose
• The base adsorption is used to determine the “ minim per gram “ factor (M/g) of
the solids .
• The minim per gram factor is (the volume in minims that is occupied by one gram
of the solid plus the weight of liquid base(BA) required to make a capsulatable
mixture).
• Or volume of mixture in minim required for solid drug to produce a mixture which
can be capsulated.
• Example of liquid base is vegtable oil, PEG 400, Polysorbate 80, Glyceryl
monooleate.
• The minim per gram factor is calculated by dividing the
weight of base plus the gram of solid(BA+S) by the
weight of mixture(W) per cubic centimeter or 16.23
minims (V).
• The lower the base adsorption of the solid and the
higher the density of the mixture, the smaller the
capsule will be.
