Definition

"Capsules are solid dosage forms in which

drug substance is enclosed within a hard or
soft shell generally made up of gelatin"
Ease of use due to the fact that it is smooth, slippery
and easy to swallow.
Suitable for substances having bitter taste and unpleasant
odor.
As produced in large quantities it is economic, attractive
and available in wide range of colors.
Minimum excipients required.
Little pressure required to compact the material.
Unit dosage form.
Easy to store and transport.
Not suitable for highly soluble substances like
potassium chloride, potassium bromide,
ammonium chloride, etc
Not suitable for highly efflorescent or
deliquescent materials.
Special conditions are required for storage.
Hard- Gelatin Capsules

Soft- Gelatin Capsules

 Hard Gelatin Capsules

“Hard-Gelatin capsules, are

typically made using gelatin and
contain dry powdered
ingredients”

These are made in two halves:

• Lower-diameter "body" that
is filled
• Then sealed using a higher-
diameter "cap".
Soft Gelatin Capsules

Soft-gelatin capsules,
primarily used for oils and
for active ingredients that
are dissolved or
suspended in oil.
 Capsules can be Made From
1. Animal protein, mainly gelatin
2. Plant polysaccharides or their derivatives like
carrageenan and modified forms of starch and cellulose.

Other ingredients can be added to the gelling agent solution

like:
▪ Plasticizers such as Glycerin or Sorbitol to
decrease the capsule's hardness,
▪ Coloring agents,
▪ Preservatives,
▪ Disintegrants,
▪ Lubricant
1. Gelatin
2. Certified dyes
3. Sugar
4. Water - 12 to 15 % but may vary depending on the
storage condition
5. Sulfur dioxide (0.15%) - prevent decomposition
during manufacture
6. Opaquants /Opacifying agent - titanium dioxide
➢ Gelatin or gelatine (from Latin: gelatus meaning
"stiff", "frozen") is a translucent, colourless, brittle
(when dry), flavourless foodstuff, derived from
collagen obtained from various animal by-products.
➢ It is commonly used as a gelling agent in food,
pharmaceuticals, photography, and cosmetic
manufacturing.
➢ Gelatin is an irreversibly hydrolyzed form of collagen
 TYPE-A
a. Derived from acid treated precursor that exhibits
an iso-electric point at pH-9.
b. It is manufactured mainly from animal bones

TYPE-B

a. Derived from alkali treated precursor that exhibits

an iso-electric point at pH-4.7.

b. It is manufactured mainly from pork skin

https://www.youtube.com/watch?v=6bYIow9p
c6M

GELITA - How is Gelatin made?

 Additional Specifications for Gelatin

1. Bloom or Gel Strength

Is a measure of the cohesive strength of the
crosslinking that occurs between gelatin molecules
and is proportional to the molecular weight of the gelatin.
Bloom Strength may vary as per the individual
requirements.
Range: 150-250 gm
Bloom is determined by measuring the weight in grams
required to move a plastic plunger of 0.5 inches in diameter, 4
mm into a 6.67 % gelatin gel that has been held at 10°C for 17
hrs without breaking.
 2. Viscosity

It is determined on a 6.67% concentration of gelatin in water

at 60°C

Low viscosity with high Bloom gelatin are used for capsulation
of hygroscopic vehicles or solids.
3. Iron Content
 HARD GELATIN CAPSULES
▪ Also referred to as “DFC” Dry Filled Capsule.
▪ CAPSULE SIZES:
▪ For human use, empty capsules ranging in size from 000 (the
largest) to 5 (the smallest) are commercially available.
▪ Generally encapsulates between 65 mg to 1 gm of powdered
material.

▪ For veterinary use: No's 10, 11 and 12 having capacities of 30,

15 and 7.5 g, respectively
 MANUFACTURING OF HARD GELATIN CAPSULES

• Steps involved in making empty gelatin capsules

with peg/pin method…
1. Dipping
2. Spinning
3. Drying
4. Stripping
5. Trimming and Joining
6. Polishing
▪ DIPPING : Pairs of the stainless-steel pins are dipped
into the dipping solution to simultaneously form the caps
and bodies. The dipping solution is maintained at a
temperature of about 50 degree centigrade in a heated,
jacketed dipping pan.

▪ SPINNING: The pins are rotated to distribute the gelatin

over the pins unifomly and to avoid the formation of a
bead at the capsule ends.
▪ 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 to remove water.

▪ 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. After trimming to the right length, the
cap and body portion are joined and ejected from the
machine.
▪ POLISHING
Pan Polishing : Acela-cota pan is used to dust and polish. A
polyurethane or cheese cloth liner is placed in the pan, and
the liner is used to trap the removed dust and to impart gloss
to the capsule

Cloth Dusting : Capsule are rubbed with cloth.

Brushing : Capsule are feed under soft rotating brush.

capsule preparation process

https://www.youtube.com/watch?v=_eoPLQ6j
yUY
 Factors affecting Capsule Preparation
▪ During production the thickness of the capsule wall is
controlled by the viscosity of the gelatin solution, speed and
time of dipping.
▪ Empty capsules should not be subjected to temperature
above 38ºC (might destroy the capsule shells such that they
can not be handled in the Filling Equipments)
▪ Empty capsules should maintain moisture Content between
12% and 15%. Below 10% they become brittle Above 16%
they might increase in size (causing problems in the filling
equipment) or they might become soft.
 Capsule Filling
1. Dependent type- Powder is transferred from a
hopper directly to the capsule body and flow of the
powder is aided by a revolving auger or by vibrating
plate.
2. Independent type- Compress the measured amount
of powder to form a slug. The slug is formed inside
the dosator or dosing tube with the help of movable
piston that controls the dosing volume.
Common working principle of all capsule filling
machines?
Powder from the storage hopper

Separation of body and cap of the capsules

Filling into empty part of body

Close the body with cap

Eject the filled capsule by chute

 Hard capsule FILLING

1) Bench scale filling.(for small scale filling)

- Manual filling machine
eg: Feton capsule filling machine

2) Industrial scale-filling.
Comes in varying shapes and sizes
- semi automatic machine
- fully automatic machine
➢ Used for filling a small number of capsules in the
pharmacy, at the prescription counter
➢ The ingredients are triturated to fine & uniform
powder.
➢ The powder is placed on a powder paper or
ointment slab and smoothed with a spatula to a
height approximately half the length of the capsule
body
1. The base of the capsule is held vertically and the open end is
repeatedly pushed or "punched" into the powder until the
capsule is filled;
2. The cap is then replaced to close the capsule. Each filled capsule
is weighed using an empty capsule as a counterweight.
3. Powder is added or removed until the correct weight has been
placed in the capsule.
4. The filled capsule is tapped so that no air spaces are visible
within the contents
 HAND OPERATED CAPSULE FILLING MACHINE

✓It consist of a bed having 200-300 hole, a loading tray

having 200-300 holes, a powder tray, a pin plate having
200-300 pins, a sealing plate having a rubber top, a
lever, a cam handle.
✓The empty capsules are filled in the loading tray and
it is placed over the bed. The cam handle is operated
to separate the capsule caps from their bodies.
✓The powder tray is placed in a proper position and
filled with an accurate quantity of powder with
scraper. The excess of the powder is collected on the
platform of the powder tray. The pin plate is lowered
and the filled powder is pressed by moving the pin
downwards.

✓After pressing the pin plate is raised and the remaining

powder is filled into the bodies of the capsules. The
powdered tray is removed after its complete filling. The
cap holding tray is again placed in position. The plate
with the rubber top is lowered and the lever is
operated to lock the caps and bodies. The loading tray
is then removed and filled capsules are collected.
Sealing plate with rubber top Pin plate with 200-300 holes

Bed – 200-300 holes

Cam handle

Powder tray

lever
loading tray
with 200-300 scraper
holes
 Semi-Automatic Capsule Filling Machine
There are 3 stations in this semi-automatic capsule
filling machine

1. Orientation of capsule

2. Powder filling

3. Capsule closing.
 Orientation of Capsules

The functions of first station include :

1. capsule feeding

2. Aligning

3. insertion into bores of holding ring

4. vacuum application for separating capsule cap and body .

5. After orientation of capsule, capsule cap can stay in upper

holding ring and capsule body can stay in lower holding ring.
 Powder Filling

1. Separate the holding ring,

2. put the lower (body) holding ring on the rotary
table, pull the powder hopper over the lower
(body) holding ring,
3. then auger inside powder hopper starts to run
and fill powder into the capsule body.
4. While lower holding ring turns one circle, push
powder hopper to its original position.
 Capsule Closing
1. Put upper holding ring and lower holding ring
together,
2. then position intact holding ring in front of peg ring .
3. closing plate is pivoted to a position approximately
180 degrees
4. Pneumatic pressure is applied to peg ring which finally
push capsules inside the bores of holding ring
5. the finished capsules will be collected into the
container.
Semi-Automatic Capsule Filling Machine

https://www.youtube.com/watch?v=JIGGKDVa
ZrU
 AUTOMATIC CAPSULE FILLING MACHINE

• Automatic Capsule Filling Machine has been designed

and developed to fill hard gelatin capsules with
powder or pellets.
• It is an extremely durable and reliable machine that
fills dosages to the highest accuracy.
• It can be applicable to the widest range of capsules at
all sizes and guarantee the integrity of all capsules.
Fully automatic
https://youtu.be/p9xj1-kqqe4
▪ The housing and surface are covered with stainless
steel 304. All contact parts of medical powders are
made from a corrosion resistant stainless steel 316.
▪ Parts are made by CNC computer machine. All parts
are standardized and easy to substitute.
▪ Capable of filling 6 capsules at a time with operation
from 10 stations. Accurate operation for orientation,
opening, filling, joining and ejecting of the capsules
▪ Compulsory spiral feeding in the powder hopper to
ensure powder feeding and filling.
▪ Dual capsule-opening design to ensure all capsules
are opened.
▪ Electrical impact protection device to prevent any
further damage. The machine will stop automatically
in the event of collision.
▪ Safety Sensing System to shut the machine down automatically
in the event of problems when no capsules, no powder, door is
opened, and abnormal load for the machine are detected.
▪ Automatic vacuum removal of the air in the dosing tube to give
more accurate weight of the filled capsules.
▪ Exclusive dosing tube system, temperature of the powder will
not rise during the filling process.
▪ Adjustable compression piston in dosing trube to adjust the
powder volume without change parts.
At present about 9 manufacturing companies supplies the capsule
filling machines with different models.
▪ Eli Lilly and company indianapolis IN
▪ Farmatic SNC, Bologna, Italy
▪ Macofar SAS, Bologna, Italy
▪ Hofliger and Karg, Waiblingen, Germany
▪ mG2 S.P.A., Bologna, Italy
▪ Osaka, Osaka, Japan
▪ Parke-Davis and company, Detroit, MI
▪ Perry Industries, Green BayWI
▪ Zanasi Nigris, S.P.A., Bologna, Italy
Lilly capsule filling Rotofil
machine
Farmatic 2000/15, 2000/30 and
2000/60
Hofliger and Karg GKF-303, GKF-602,
GKF-1500 and GKF-2500
Macofar MT-12, MT-13/1 and MT-
13/2
mG2 G36, G37N, G38
Osaka R-180
Perry Accofil
Zanasi 6E, 40E
Hard gelatin capsules are stored in a tightly closed glass
or plastic containers, protected from dust and extremes
of humidity and temperature.

Minimum Ideal Maximum

Relative 40% 50% 60%

humidity
Temperature 15 °C 20°C 25 °C
▪ These capsules contain 12-16% water but water
content vary according to the storage conditions.
▪ Capsules become brittle in low humidity but are
flaccid and lose their shape if stored in high humidity.
▪ They do not protect hygroscopic materials from
atmospheric water vapor as moisture can diffuse
through the gelatin wall. When storage temperature
condition is high the quality of the hard gelatin
capsules are affected
 In-process quality control tests for
capsule

a. In-process quality control tests for capsule drug products are

carried out at predefined intervals during the product
manufacturing, by the manufacturing personnel, and their
results recorded on the batch record.
b. Adverse findings in these tests can be used as a guide to
altering the manufacturing-process parameters.
For Hard Gelatin:
Visual inspection, fill weight, and fill-weight uniformity are the
key in-process tests used for hard gelatin capsules.
For Soft Gelatin:
1. Gel ribbon thickness and uniformity across the ribbon
2. Soft-gels seal thickness at the time of encapsulation
3. Moisture level of the capsule shell before and after drying
4. Weight of the capsule shell and its variation from capsule-to-
capsule
5. Weight of the capsule fill and its variation from capsule-to-
capsule
 Finished product
quality control tests
for capsule
 1. Permeability and sealing
a. Hard gelatin capsules are tested for any
breach of physical integrity (breakage or
opened cap and body).
b. Soft gelatin capsules are tested for physical
integrity (absence of leakage) by visual
inspection.
 2. Potency and impurity content
a. All capsules are tested for drug content
(potency, as a percent of label claim).
b. In addition, most drug products are tested for
related substances or impurities.
c. These must meet predefined specifications for
a batch to be acceptable.
 3. Weight Variation Test
Weigh 20 intact capsules individually and determine the
average weight

The test passes, if individual capsule falls within the

range of 90-110 % of average weight

1. Rotoweigh: High speed capsule weighing machine (73000

capsules per hour) sold by Eli Lilly. Measures the reflected
energy.
2. Vericap 1200: (73000 capsules per hour) Sold by Modern
controls. Measures change in dielectric constant.
 4. Content Uniformity
30 capsules are selected, out of which 10 are
assayed as per the procedure given in monograph

The test passes, if 9 of the 10 are within the specified

range of 85 to 115 %

If 2 capsules are outside the range, then repeat the

procedure on remaining 20 capsules.

The test passes, if 28 of the 30 are within specified range

of 85 to 115 %
 5. Uniformity of weight
Weigh the 20 intact capsule individually

Remove content from each capsules and take weight of empty shell

Determine the capsule weight content using following formula

Weight of content= weight of intact capsule- weight of empty shell

Determine avg wt.

Avg wt. of content variation allowed
For less than 300----10%,
For 300 mg or more----7.5%
 8. Moisture permeation test
• The USP requires determination of the moisture-permeation
characteristics of single-unit and unit dose containers to assure
their suitability for packaging capsules.
• The degree and rate of moisture penetration is determined by
packaging the dosage unit together with a colour-revealing
desiccant pellet,
• exposing the packaged unit to known relative humidity over a
specified time, observing the desiccant pellet for colour change
(indicating absorption of moisture) and comparing the pre-test
and post-test weight of the packaged unit.
 9. Microbial content
1. The capsules are tested to ensure lack of growth of bacteria
and mould by microbiological tests.
2. These tests are usually carried out by incubation of the capsule
contents in a growth medium and counting the colonies
formed after a predefined period of time.
3. Selection of the growth medium and duration of the test, as
well as maintenance of aseptic conditions during the testing,
are critical to successful assessment of microbial
contamination by this method.
 10. Shelf-life test
These tests are frequently carried out after defined periods of storage at
predetermined conditions. They help to assign and verify the shelf life and
usability of the drug product.
Stability testing of capsules
1. Stability testing of capsules is performed to determine the physicochemical
stability of the drug substance in the finished drug product under specified
package and recommended storage conditions intrinsic stability of the
active drug molecule and the influence of environmental factors (e.g.,
temperature, humidity, light), on formulation components, and the
container and closure system.
2. The stress-testing, long-term stability and accelerated stability tests help to
determine the appropriate storage conditions and the product’s anticipated
shelf life.
Soft Gelatin
Capsules
“Soft gelatin capsules are one piece, hermetically
sealed, and are made up of gelatin in which
glycerin or polyhydric alcohol (sorbitol) are
added.
Liquid or suspension or semisolid are enclosed in
a matrix of soft gelatin capsules.”
➢ They may be oblong, oval, or
round.
➢ They Vary in sizes
➢ They may be single colored or
two toned
 Maximum capsule size and shape convenient for oral
human use is:
 20 minim oblong
 16 minim oval
 9 minim round
▪ Drug present in these capsules filled in the form of
suspension, solution or emulsion.
▪ Ingredients that are solid at room temperature can
also be encapsulated in softgels by accogel capsule
filling machine.
▪ The softgels can be coated with enteric resistant or
delayed release coating material.
 Types of soft gels
➢ Orally administered: Solutions or suspensions that release contents in
stomach.

➢ Chewable softgels: Highly flavored shell is chewed to release drug liquid fill
matrix.

➢ Suckable softgels: gelatin shell to be sucked to release liquid matrix

➢ Meltable softgels: meltable soft gels are used for pessaries or suppositories.
The capsule shell is basically made up of
Gelatin,
plasticizer
and water.
It may contain additional ingredients such as
preservative, coloring & opacifying agents, flavoring
agents, sugars, & medicaments to achieve desired
effects
1. Capsule shell WATER: NOT MORE THAN 45% w/w, the
ratio by weight of water to dry gelatin can vary from 0.7 to
1.3 depending on the viscosity of the gelatin being used.

2. PLASTICIZER: Used to make the soft gel shell elastic &

flexible. Ratio used is in-between 0.3 to 1.8 for soft to hard
shell on dry basis. E.g. glycerin , sorbitol

3. COLOUR: Used in shell has to be darker than color of

encapsulating material. colors may be natural or synthetic.
4. OPACIFIER: Usually titanium dioxide, may be added to produce
an opaque shell ,when the fill formulation is a suspension or to
prevent photo degradation of light sensitive fill ingredients.
Concentration of opacifier may be up to 0.5 %
5. Chelating Agents: Iron is always present in raw gelatin, &
capsule shell should not contain iron more than 15 ppm.
Additionally chelating agent may be used for preventing the
reaction of iron with organic materials or colors.
 Typical Formula for Gelatin Sheet

• A typical gel mass formula for making soft gelatin capsules would
be:
1. Gelatin 35-45%
2. Plasticizer 15-25%
3. Water ~ 40%
4. Dye / Pigment as per need
5. Opacifier as per need
6. Other (flavor, sugar,) as per need

(1 part gelatin, 1 part water, 0.4-0.6 part plasticizer)

 Gelatin Mass Manufacture
➢ The gel is prepared in a 300-litre stainless steel
vessel
➢ Gelatin powder is mixed with water and glycerin.
➢ Then Heat and stirred to form molten gelatin mass.
➢ Transfer it into 200-kg mobile vessels
➢ Then mixed using Turbine mixer, where colours and
flavors can be added.
➢ This mass is kept at a constant temperature until it is
needed for the next stage of the process.
 MANUFACTURE OF SOFT GELATIN CAPSULES

 Plate process.

 Rotary die process.

 Reciprocating die

 Accogel machine (unique equipment that

accurately fills powdered dry solids into S.G.C.).
 1. Plate process:
• Gelatin sheet is placed over die plate containing
numerous die pockets,
• Application of vacuum to draw the sheet in to the die
pockets,
• Fill the pockets with liquid or paste,
• Place another gelatin sheet over the filled pockets,
and
• Sandwich under a die press where the capsules are
formed and cut out.
• Robert P scherer in 1933 invented this method
• the material to be encapsulated flows by gravity

<<Principle>>

• “Involves the formation of a heat seal between two

gelatin ribbons, simultaneously with filling of dosing
liquid into each capsule”
 Typical Parts of Rorary die Machine
1.Spreader Box
2.Cooling Drum
3.Oil Lubrication Roller
4.Gelatin Ribbon Guide Roller
5.Die Roll
6.Medicine Filling Hopper
7.Medicine Filling Pump
8.Injection Wedge
9.Capsule Stripper
10.Conveyor
 The following parameters should be
monitored/controlled during manufacturing:

Gelatin temperature
Fill liquid temperature
Ribbon thickness
Seal or seam width
Fill liquid quantity
pressure between rotary dies (controls softgel
shape and final cut out from gel ribbon)
• Also known as Stern machine, uses a system of rotary dies but
is unique in that. it is only machine that can successfully fill dry
powder into a soft gelatin capsule.
1. Measuring roll- for filling powder or granular material under
vacuum. Measuring roll rotates directly over the die roll, and
the pockets in the 2 rolls are aligned each other.
2. Die roll- plasticized gelatin sheet under vacuum.
3. Sealing roll- second gelatin sheet applied to form other half of
capsule. Pressure developed between die roll and sealing roll
seals and cut out the capsules.
 Base Adsorption and Minim per Gram Factor
1. determined when the soft gelatin capsule shell contains
suspension then it become crucial to find minimum quantity
of base/insert liquid/vehicle is required to prepare the
suspension.
2. Base Adsorption is defined as the minimum amount of base
or vehicle in grams required per gram of solid drug to form a
mixture which easily can be encapsulated in soft gelatin
capsule.
3. Base adsorption = Weight of base(g)/Weight of drug(g).
4. It is a unit less value because both parameters are in grams.
Minim per Gram Factor
It defined as volume of mixture in minims required for a solid
drug to produce a mixture which can be encapsulated.
M/G factor = (BA+S) ÷ D
BA : weight of liquid Base
S : 1 gm of Solid
D: Density of mixture.
Example- M/G =50, means 1g of drug in a mixture occupies 50
minims.
1ml =16.23 minims.
Quality control
tests for soft
gelatin capsules
 In Process Test
1. Gel ribbon and uniformity
thickness across the ribbon
2. seal thickness
3. Weight of capsule fill and its variation from capsule to
capsule
4. weight of capsule shell and its variation from capsule to
capsule
5. Moisture level of the capsule shell before and after drying
1.Uniformity of dosage unit
2.uniformity of content
3.uniformity of mass
4.dissolution
5.Storage
6.labelling
1. Permeability and sealing
2. potency and impurity content
3. average weight and weight variation
4. uniformity of content
5. Disintegration
6. Dissolution
7. moisture content
8. microbial content
1. permeability and sealing:
capsules are tested for physical integrity, by
visual inspection like, absence of breakage or
open cap and body

2. Potency And Impurity Content:

All capsules are tested for drug contents, as
well as impurities and other substances must
meet pre-defined specifications for a batch
to be acceptable
❑ capsules are tested to ensure lack of
growth of bacteria and mold by
microbiologiocal testing.
❑ test is carried out by incubating the capsule
contents in growth medium and counting
colonies formed after pre- defined period of
time.