INDUSTRIAL PHARMACY

UNIT 3

Capsules
 Capsules - Capsules are the solid dosage forms
consisting of single dose of drug enclosed in a small
container or shell of a suitable form of gelatin.
It’s available in many sizes to provide drug flexibility
There are two types of capsules
1. Hard gelatin capsules
2. Soft gelatin capsules

➢ Hard gelatin capsules – Hard gelatin capsule is a type

of capsule are used for administration of powders / solid
medicaments.
It consists of two part
a. Body b. Cap
The drug is filled in the body part over which the other
half is fitted as a cap.
• Advantages
1. Easy to swallow
2. Easy to handle and carry
3. Different sizes are available
4.Therapeutically inert & easy to digest
5. Protection of medicament
• Disadvantage
1. Hydroscopic drug is not suitable for filling into the
capsule
2. Cross linking can affect hard gelatin.
3. Slower production rate
4.Efflorescent substance may cause to capsule too soft

• PRODUCTIONOF OF HARD GELATIN CAPSULE

1. Dipping - 150 pairs of these pins are dipped, into a

gelatin sol" of controlled viscosity to form caps and
bodies simultaneously.

2. Spinning - The pins are usually rotated to distribute

the gelatin uniformly

3. Drying - The pins are moved through a series of

controlled air-drying kilns for the gradual and
precisely controlled removal of water

4.Stripping - A series of bronze jaw strips the cap and

body portion of the capsule from mold pins
5. Trimming & joining - After that stripped cap and body
are trimmed as per required length by knife after
trimming cap and body are joined together

6. Polishing - At least gelatin shall polish with the help of

cloth, brush and pan polishing

• FLLNG CAPACTTY OF HARD GELATIN CAPSULE

1. Empty capsules are sold by sizes.

2. The ones most commonly employed for human use
range from size 0, the largest, to size 5, the
smallest
• PREPARATIONOF FILLED HARD GELATIN
CAPSULE

1. Filling the Capsule shells

Manual punch machine
Automatic & Semi-automatic

Capsule sealing - Machine linked with filling machine.

Banding - Two capsule parts are sealed with gelatin
band.
Contact area seal by water and ethanol and thermally
bonded at 40-450°C

Cleaning & Polishing - After filling some powder

formulation may adhere outside capsule they may be
removed by cleaning & polishing.

• FILLING OF CAPSULE

a. Loading of empty shell in filling machine – First of all

empty capsule shells are placed into the shall hopper of
capsule filling machine
b. Correction of shall – In this step we align the capsule in
right direction (their caps turned up and bodies down)

c. Separation of the Cao and body – after that cap and

bodies of gelatin shall separated

d. Filling of body with formulation – In this step API &

Excipient mixture weighed and filled in body

e. Attachment of body & cap – After filling body cap

rejoined together

f. Ejection of filled capsule – At least filled capsule are

ejected from the machine and collected in container

• MANUFACTURING DEFECTS

1. Colour deviation - Relative bad stability of selected dyes

and pigments

2. Short body/cap - Insufficient entry of the body/cap

into the collet prior to cutting operation due to wet shell
or problem with the collet.
3. Long body/cap - Caused by a missing knife/broken
knife during cutting operation.

4.Dots/specks - Small fragments of shell walls generated

during the trimming process getting into the dipping
area. This happens during the mold dipping process.
Could also be result of a print.

5. Double cap - Loose cap fits over the body of another

capsule after one of the caps is loose due to insufficient
pre-lock position in joining block. This happens during
handling of capsules.

6. Rough cut - Caused by a blunt knife during cutting

operation

7.Star ends - uneven distribution of gelatin on dip-

coated pins or an excessive amount of gelatin solution
on the end of the pin.

8. Bubbles - Improper vacuum or duration of the gelatin

bubbles extraction process.
 9. Damaged print - Improper ink viscosity and applying
pressure uneven flow of the ink, clogged ink jets,
incomplete drying of ink etc.

10. Thin/thick wall - uneven distribution of gelatin on dip-

coated pins (thin wall). Pins are dipped twice or are in
gelatin too long (thick wall).

11.Split - Caused by uneven drying or an uneven film

thickness at the point of split

➢ Soft gelatin capsules – Soft gelatin capsules are one

piece sealed soft gelatin shell that used for filling liquid,
semisolid or suspension
The soft gelatin shell made up for - Gelatin, Water,
Glycerin, Sorbitol

• ADVANTAGES OE SOFT GELATIN CAPSULES

1. Better bioavailability
2. Rapid absorption
3. Masking taste and odour
4.Precise dosing
5. Easy to swallow
• DISADVANTAGES OF SOET GELATIN CAPSULES
1. Moisture-sensitive
2. Limited fill material
3. Higher cost
4.Production complexity

• Base adsorption - The number of grams of liquid base

required to produce a capsulatable mixture when mixed
with 1 gm of solid
(M/G) = (BA+S) x V/w
Base Adsorption = Weight of base / Weight of Solid

• PREPARATION OF SOFT GELATIN CAPSULES

1. Plate Process
2. Rotary Die Process

1. Plate Process - The plate process is the oldest

commercial method of manufacture, but today this
equipment can no longer be purchased, and
consequently. only a few companies still use this
process
 Plate process-a batch process- involves pressing two
sheets of wet gelatin together between two molds,
provided with depressions.
One of gelatin sheet is placed over mold
A second gelatin sheet was laid over the first and both
were pressed together with fill material sandwiched in
between.
The pressure of the plate sealed the top and bottom
sheets of gelatin together.

• ADVANTAGES OF PLATE PROCESS

1. Easy to undertake
2. Easy to operate
3. Doesn't require a very skilled person for operating this
machine.

2. ROTARY DIE PROCESS - The process of making a

soft gelatin capsule using a Rotary Die machine.
an equipment that is used in filling gelatin shells
with liquids, suspensions or semisolids.
 CONSTRUCTION
1. The machine used for the process contains two hoppers,
one for the hot liquid gelatin mix while the other for the
semi-solid or liquid fill.
2. There are two rotating dies containing cavities of
desired shape and size which rotate in opposite
directions.
3. The soft gelatin capsules are prepared and then filled
immediately with the liquid medicaments.

WORKING
1. Liquid gelatin mixture is placed in one hopper and the
liquid medicament in the other hopper.
2. There are two rotating dies which rotate in opposite
directions.
3. When fluid gelatin mixture enters into machine, it
produces two continuous ribbons
4.These ribbons come over the rotating dies from opposite
directions & enter in between dies. Thus, half shell of
the capsule is formed.
5. At this stage measured quantity of medicament is
filled into it with stroke of pump.
6. With the subsequent movement of the dies.
7.The other half of the capsule is formed.
8. Two halves of capsules are sealed together by heat &
pressure of rotating dies.

• EVALUATION OF CAPSULES

1. API percentage test – This test is perform to ensure the

average amount of API in capsule according to
monograph
+/- 5% to +/- 10% limit allowed
This test is common for both hard and soft capsule

2. Weight variation test – This test is perform to

maintain the equal weight of each and every capsule
In these test 20 intact capsules are first weighed
individually & then weighed after removing their
contents Difference between two weights gives weight
of contents. Not more than two capsules should deviate
from average weight of the contents

3. Content uniformity test – This test is perform to

ensure for each and every capsule contain equal
amount of drug substance
 30 capsule selected randomly
From them only 10 assayed – for first stage if first
stage fails then additional 20 capsule assayed by
suitable analytical method
85% - 115% of labelled limit to allowed for individual

4.Disintegration test - This test for capsules is similar to

that used for testing of tablets. Test is not applicable to
modified release capsules & capsules for which
dissolution test is prescribed. The hard gelatin capsules
are expected to disintegrate within 30 ABL INE
minutes while the soft gelatin capsules in minutes
unless otherwise specified, when water is used as the
testing fluid.

5. Dissolution test – This test for capsules is essentially

similar to that followed for tablets with the acceptance
criteria also being the same as that for capsules.
However, where the capsule shells are found to interfere
with the analysis. Necessary correction can be made
by dissolving the empty shells of not less than 6
capsules in the specified volume of dissolution
medium.
• PACKING AND STORAGE OF CAPSULES

1. Capsules should be packed in well-closed glass and

stored at a temperature not exceeding 30°C.
2. Capsules can be individually protected by enclosing
them in a strip or blister packs.
3. The contents are removed from the strip packs by
tearing / cutting to separate capsules.
4.A press on blister forces the capsule through the
backing strip.
5. They should comply with storage requirements in the
pharmacopoeia of India.

• APPLICATION OF CAPSULES

1. Enteric coated capsule – The hard and soft capsules

prepared in such a manner that shells resist the action
of gastric fluid but are attacked by the intestinal fluid
to release the contents.
resist the action of gastric fluid but are attacked by
the intestinal fluid to release the contents.
2. Chewable capsules - Chewable soft gelatin capsules are
soft gelatin capsules designed to release the active
ingredients in the mouth.
Some of the capsules dissolve completely in the mouth
while some others leave a residue of a water-insoluble
gum

3. Modified release capsules - Hard or soft capsules in

which the contents or the shell or both.
A prepared by a special process designed to modify rate
at which active ingredients are released.

4.Rectal and vaginal capsules - soft gelatin capsules

provide a good substitute for rectal and vaginal
suppositories.

5. Ophthalmic capsules - soft gelatin capsules provide a

useful and economical unit dosage pack for
ophthalmic ointments.

➢ PELLETS - In pharmaceutical industries, pellets are

multi particulate dosage form which was formed by the
agglomeration of fine powdered excipient and drugs
 together that leads to the formation of small free
flowing spherical or semi spherical particles.

• ADVANTAGES OF PELLETS
1. Uniformity of dose.
2. Excellent flow properties
3. Improves aesthetic appearance of products.
4.Bitter taste
5. Reduced risk of dose dumping

• DISADVANTAGES OF PELLETS
1. Time consuming process.
2. Higher cost of production.
3. Personal needed for manufacturing.
4.Requires highly specialized equipment.
5. Lack of manufacturing reproducibility and efficacy

• FORMULATION REQUIREMENTS OF PELLETS

Formulation aids or excipients are added to
pharmaceutical dosage forms for satisfactory delivery
of the drug to the target site, to impact favourable
 features to the dosage form, and to facilitate product
manufacture.
1. Fillers - Are used to add bulk or weight to the products.
eg. - Microcrystalline cellulose (MCC), Starch, Sucrose

2. Binders - Added to bind powder & makes the pellet

integrity.
eg. - Hydroxypropyl methylcellulose (HPMC),
Hydroxypropyl cellulose (HPC), Gelatin.

3. Lubricants - Added to reduce friction between particles

and surface of equipment.
eg. Glycerine, Polyethylene glycol (PEG), Magnesium
or Calcium stearate.

4.Disintegrating agents - Break down of pellets when

ingested.
eg. Alginate, Cross carmellose sodium.

5. PH adjuster - A pH adjuster is a chemical used to alter

the pH or Potential Hydrogen level.
eg. Citrate, Phosphate
6. Separating agents - Attracted to each other, separating
agents promote separation of pellets into separate unit.
eg. Kaolin, Talc, Silicon dioxide.

• Pelletization process – The process of formation of pellets

from fine powder of API + excipient is called
pelletization
1. Direct pelletization
2. Agitation
3. Cryopelletization
4.Powder layering solution / suspension layering
5. Extrusion - spherization
6. Globule/ droplet formation
7.Freeze pelletization

1. Direct pelletization - In direct pelletization technique,

pellets am manufactured directly from powder with a
binder or solvent.
This process is fast and requires less auxiliary
materials.
By this technique, compact and round pellets of
diameter between 0.2 1.2mm are obtained.
 Such pellets am ideal for automatic dosing and
uniform coating.
Pellets have a density higher than the spray granulates
and agglomerates.

2. Agitation - Agitation is also known as spherical

agglomeration.
In spherical agglomeration process, suitable quantity of
liquid is added before or during agitation to the finely
divided particles to convert into spherical particles by a
continuous rolling or tumbling action.
Spherical agglomeration can be divided into liquid-
induced and melt induced agglomeration. Since many
years spherical agglomeration is carried out in
horizontal drum pelletizer, inclined dish pelletizer, and
tumbling blenders.

3. Cryopelletization - In the process of repalletization,

liquid nitrogen is used as a fixing medium to convert
the droplets of liquid formulations into solid spherical
particles or pellets. Technology initially developed for
lyophilization can be used to produce drug-loaded
pellets in liquid nitrogen at 160°C temperature.
• The procedure allows instantaneous and uniform
freezing of the processed material due to the rapid heat
transfer between the droplets, and thus the large surface
area facilitates the drying process
• The amount of liquid nitrogen required for
manufacturing a given quantity depends on the solid
content and temperature of the solution or suspension
being processed.

4.Freeze pelletization - A molten solid carrier or matrix is

introduced in the form of droplets into an inert column
containing a liquid in which the molten solid carrier is
immiscible.
The molten solid carrier move upward or downward in
the liquid column depending on the density of the
molten solid carrier with respect to the liquid in the
column, and then solidify into pellets.
If the density of the carrier is less than the liquid, the
carriers are introduced as droplets from the top of the
column and the pellets are formed at the bottom.
If the density of the carrier is more than the liquid, the
carriers are introduced as droplets from the bottom of
the column and the pellets are formed at the top.
• EQUIPMENTS FOR MANUFACTURING OF
PELLETS

1. Supply bins - The supply bins located ahead of the

pellet mill, should store a sufficient quantity of feed to
provide a continuous operation of the pelleting unit and
also a continuous operation of the mixer which provides
mash to the pelleting unit.
The supply bin constructed from stainless steel should
have at least two bins, results in an efficient mixing as
well as pelleting.

2. Pellet mills - The thoroughly mixed ingredients flow

into a flow rate regulator called a feeder under gravity.
It is equipped with speed controlling devices, provides a
constant, controlled and uniform flow of feed to the
mixing and pelleting operation, and variation in this
flow leads to poor conditioning and a variable product.

3. Coolers - The pellets from the pellet mill flow under

gravity into a device for cooling and drying. When
pellets leave pellet mill, they are at very high temp.
(190°F) & also have high moisture content (17- 18%)
4.Crumble rolls - A crumbling process should be used for
producing pelleted feed particles smaller than 10/64.
In this process, small pellets are broken between two
powered corrugated rolls, placed below the cooler.
A crumbling roll has heavy steel frame and housing.
The corrugated rolls are 8-12 inches in diameter and 72
inches long.

5. Shaker - The product (either whole or crumblised) from

crumbling device is passed to a shaker (screening
device) that extracts the undesirable undersized
portions of product from correctly sized material.
The undersized product is returned to the pellet mill for
repelletisation and is termed recycle or fines.

6. Pellet elevating systems - The correct sized product in

its finished form is obtained from the shaker and is
ready for packaging or shipment.
In many mills, the pellet shaker is located on the upper
floors of the unit so that the screened product, the
oversize crumbles, and the fines flow under gravity to
their correct destination.
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