8/12/2022 Umar Farooq 1

capsules
The word capsule is derived from the Latin word ‘Capsula’ which
means
a small box or container.
► Capsules are solid dosage forms with hard
or soft shells. They are of various shapes
and sizes, and contain a single dose of one
or more active ingredients. They are
intended for oral administration.
► In capsules the drug is enclosed within hard
or soft shell.
Capsule shells are made of gelatin or other
substances, the consistency of which may
be modified by the addition of substances
such as glycerol or sorbitol.

The shell should disintegrate in the

presence of digestive fluids so that the
contents are released.
The contents should not cause
deterioration of the shell.
 Excipients for production
of the Capsule shells :
diluents,
solvents,
surface-active substances,
opaque fillers,
antimicrobial agents,
sweeteners,
colouring matter,
flavouring substances,
glidants,
substances capable of modifying the behaviour of the active
ingredient(s) in the gastrointestinal tract.
Categories of capsules
 hard capsules;
 soft capsules (softgels);
 modified-release capsules:
1. delayed-release capsules
(gastroresistant / enteric capsules)
2. sustained-release capsules
(extended-/prolonged release capsules).
 Type of capsules depend on
plasticizer content
and technological principle

1. Hard-Shell Gelatin Capsules;

2. Soft- Gelatin Capsules

(softgels);
Soft gelatin capsules (softgels) are hermetically
sealed one-piece capsules containing a liquid or
a semisolid fill.
Soft capsules are usually formed, filled, and
sealed in one operation.
Advantages
of soft-gelatin capsules
1. Improved bioavailability, as the drug is presented in a
solubilized form.
2. Enhanced drug stability.
3. Consumer preference regarding ease of swallowing,
convenience, and taste can improve compliance.
4. Offer opportunities for product differentiation via colour,
shape, and size and product line extension.
5. The softgels can be enteric coated for delayed release.

They are popular for pharmaceuticals, cosmetics, and

nutritional products.
 Hard capsules have shells consisting of two
prefabricated cylindrical sections that fit
together.

 and closed, and the other is open. The contents

of hard capsules are usually in solid form
(powder or granules).
In the manufacture of capsules,
measures are taken to:
 ensure that the active ingredient(s) when
present in solid state form have appropriate
solid-state properties such as particle-size
distribution and polymorphic form;
 ensure that mixing with excipients is carried
out in a manner that ensures homogeneity;
 minimize the degradation of the active
ingredient(s);
 minimize the risk of microbial contamination;
 minimize the risk of cross contamination.
Stage of capsules production:

1. Preparing of gelatin 1. Preparing of gelatin

solutions. solutions.
2. Preparing of gelatin 2. Preparing and filling
shells. of soft-gelatin
3. Hard-gelatin capsules.
capsule filling.
4. Packing and 3. Packing and
labeling. labeling.
 Methods obtaining
of gelatin solutions

Obtaining Obtaining
of gelatin solutions of gelatin solutions
with stage of without stage of
swelling swelling
HJ Series Gelatin Melting
Tank
Obtaining of gelatin solutions
with stage of swelling
1. Swelling of gelatin in water (15 - 18 °C, 1.5 - 2
hours).
2. Dissolving of gelatin.
3. Adding preservatives, plasticizers and others
excipients.
4. Remove of air bubbles from the solution of the
gelatin by the vacuum.
5. Stabilization of solution of the gelatin (45-60 °C).
Obtaining of gelatin solutions
without stage of swelling
1. Heating of purified water (70-75 °C).
2. Dissolution of preservatives, plasticizers and
others excipients in the water.
3. Dissolution of the gelatin.
4. Remove of air bubbles from the solution of the
gelatin by a vacuum.
5. Stabilization of the solution of the gelatin (45-60
°C).
Capsules sizes
 000 1000mg
 00 650mg
0 450mg
1 300mg
2 250mg
3 200mg
4 150mg
5 100mg
Shapes of capsules
 Snap fit:
Point to point attachment, straight at the point.

 Coni snap:
Slightly tappered, attached with locking roofs

 Coni snap supro:

Only lower portion could be seen, most stable and best
locked.
Coni snap
 The original Snapfit design enables the
two halves of the capsule shell to get
interlocked through the groves present of
the shell walls and thus provides reliable
closing.
Coni snap
Coni snap supro
 modified design of Coni-snap to
 ensure integrity and maximum security
against tampering. In this design,
 the upper capsule part (cap part) extends
deep over the lower part (bodypart) where
only rounded part of the later is exposed.
Hard Gelatin Capsules
The hard gelatin capsule consists of a base or body and a
shorter cap, which fits firmly over the base of the capsule .
The moisture content is about 16-25%

22 8/12/2022 Umar Farooq

Capsule Sizes
Empty gelatin capsules are manufactured in various

sizes, varying in length, in diameter, and capacity.

For human use, empty capsules ranging in size from

000 the largest, to 5 the smallest are commercially

available.

23 8/12/2022 Umar Farooq

 Preparation of Filled Hard Gelatin Capsules

The preparation of filled hard gelatin capsules may be

divided into the following steps:

1. Preparing the formulation

2. Selecting the capsule size.

3. Filling the capsule shells.

4. Cleaning and polishing the filled capsules.

24 8/12/2022 Umar Farooq

I. Preparing the formulation

Preformulation studies are used to determine if the bulk

powders may be blended together as such, or if they
require reduction of particle size or processing into formed
granules.

Dry Powder
Milling
To achieve uniform drug distribution through out a powder
mix, it is advantageous that the density and particle size of
the drug and non-drug components are similar. This is
achieved by particle size reduction (milling).
25 8/12/2022 Umar Farooq
Diluent
Generally, hard gelatin capsules are used to encapsulate

between about 65 mg and 1 g of powdered material,

including drug and any diluent required.

If the dose of the drug to be placed in a single capsule is

smaller than 65 mg to produce the proper fill, lactose,

microcrystalline cellulose, and pregelatinized starch are

common diluents used in capsule filling. But when the

amount of drug is large enough to fill a capsule completely,

a diluent may not be required.

26 8/12/2022 Umar Farooq
Lubricant
Magnesium stearate 1% is utilized to prevent adhesion

and facilitate the flow of the powder in capsule filling

machine.

Glidant
The powder mixture or granules must be free-flowing to

allow passage from the hopper by the addition of a glidant

such as 1% silicon dioxide.

Lubricant and Glidant are used to improve filling

properties.
27 8/12/2022 Umar Farooq
Wetting agent
Addition wetting agents, as sodium lauryl sulfate, in

capsule facilitate the wetting of the drug substance by

gastrointestinal fluids to enhance dissolution.

28 8/12/2022 Umar Farooq

 Liquids
Gelatin capsules are
unsuitable for water, that
softens the gelatin

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 (soft gelatin capsules)

29 8/12/2022 Umar Farooq

Granules and Pellets
Granules and Pellets are
packed in capsules instead of
powder to produce modified
release patterns.

Granules are produced by

granulation and are more
irregular than pellets which
are spherical and produced
by microencapsulation
technique 30 8/12/2022 Umar Farooq
Capsules within capsules:
If one ingredient must be separated from
others in the formulation, a small capsule,
such as a No. 5, may be filled with one
powder and placed into a larger capsule
with the remaining ingredients in the
formulation.

Tablets within capsules:

Small tablets are filled into capsules to
produce special release forms or to separate
incompatible ingredients.

This small tablet can be placed inside the capsule following the
addition of a small quantity of the powder and the filling
completed. 31 8/12/2022 Umar Farooq
Powders Granules Beads

Tablets Capsules Pastes

Liquids

32 8/12/2022 Umar Farooq

II. SELECTION OF CAPSULE SIZE
Depend upond the formulation
Size or capacity of the capsule to be selected.

The density and compressibility of a powder

The degree of pressure used in filling the
capsules.

33 8/12/2022 Umar Farooq

Determination of capsule fill weight

To determine the size of capsule to be used or the fill

weight for a formulation the following relationship is
used:

Capsule fill weight = Wt of caps+wt of powder

34 8/12/2022 Umar Farooq

III. Filling the capsule shells

1."Punch" Method

2. Hand-Operated Capsule Filling Machines

3. Automatic-Operated Capsule Filling Machines

35 8/12/2022 Umar Farooq

"Punch" Method
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

and smoothed with a spatula to a height approximately

half the length of the capsule body.

36 8/12/2022 Umar Farooq

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;

The cap is then replaced to close the capsule. Each filled

capsule is weighed using an empty capsule as a

counterweight.

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.

37 8/12/2022 Umar Farooq

hand-operated capsule machines
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. 38 8/12/2022 Umar Farooq

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 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.

39 8/12/2022 Umar Farooq
40 8/12/2022 Umar Farooq
Automatic-Operated Capsule Filling Machines

Machines developed for industrial use can automatically

remove the caps from empty capsules, fill the capsules,

replace the caps, and clean the outside of the capsules at a

rate of up to 165,000 capsules and greater per hour.

41 8/12/2022 Umar Farooq

42 8/12/2022 Umar Farooq
43 8/12/2022 Umar Farooq
SEALING of Gelatin capsules
In this process, the two capsule parts are sealed with a

gelatin or polymer band at the joint of the cap and body.

A tamper-resistant seal on hard gelatin capsules was

developed in which the
contact areas of the cap
and body are wetted
with a mixture of water
and ethanol to soften
the gelatin and then
thermally bonded at
104° to 113oF to form
the seal. 44 8/12/2022 Umar Farooq
CONI-SNAP Hard gelatin capsule
A recent innovation in capsule shell
design, where the two halves of the
capsule shells are enable to be
positively joined through locking
grooves in the shell walls.
The two grooves fit into each other
and ensure reliable closing of the
filled capsule.
Opening of such capsule is difficult
with increasing security of the
contents of the capsule.
45 8/12/2022 Umar Farooq
IV. Cleaning and polishing the filled capsules

Capsules prepared on a small scale or on a large scale may

have small amounts of the powder adhering to the outside

of the capsules.

This powder should be removed before packaging or

dispensing to improve the appearance of the capsules and to

preserve their quality of being tasteless on administration.

On a large scale, many capsule-filling machines are affixed

with a cleaning vacuum that removes any extraneous

material from the capsules.

46 8/12/2022 Umar Farooq

Another proposed cleaning method is to put the capsules in

a container filled with sodium bicarbonate, sugar, or sodium

chloride, and gently roll the container.

Then the container contents can be poured into a ten-mesh

sieve where the "cleaning salt" will pass through the sieve.

47 8/12/2022 Umar Farooq

 Soft Gelatin Capsules
Soft gelatin capsules (soft elastic gelatin capsules) or (softgels) are
prepared from continuous gelatin shells to which glycerin or a
polyhydric alcohols such as sorbitol has been added to render gelatin
elastic or plastic-like.
Soft gelatin capsules may be oblong, elliptical (oval), or spherical
round, oval, oblong, tube in shape., They may also be prepared of
single or two-tone color,

48 8/12/2022 Umar Farooq

Application of Soft Gelatin Capsules
1. Water immiscible, volatile and nonvolatile liquids such as

vegetable and aromatic oils, aromatic and aliphatic

hydrocarbons, chlorinated hydrocarbons, ethers, esters,

alcohols, and organic acids.

2. Water miscible, nonvolatile liquids such as polyethylene

glycols, and nonionic surface active agents as tween 80.

3. Solids may be encapsulated into soft gelatin capsules as

solutions in one of the suitable liquid solvents, as

suspensions, or as dry powders, granules, or pelletized

materials. 49 8/12/2022 Umar Farooq

Liquids which can easily migrate through the capsule

shell cannot be encapsulated into soft gelatin

capsules.

These materials include:

Water, above 5%, and low molecular weight water

soluble and volatile organic compounds such as

alcohols, ketones, acids, amines, and esters.

50 8/12/2022 Umar Farooq

Advantages of Soft Gelatin Capsules

1. They permit liquid medications to become easily

portable.

2. Comparing the degree of irritation or ulcerogenic

potential of soft gelatin capsule formulations with a

tablet formulation, Capsule formulations had a reduced

ulcerogenic potential when compared to the tablet

formulation.

3. Dose uniformity is optimized, because the drug is

dissolved or dispersed in a liquid which is then dosed

volumetrically
51
into8/12/2022
the capsule accurately. Umar Farooq
4. Improve drug stability by resist gaseous diffusion and

contain no water, thus protect drugs sensitive to

oxidation or hydrolysis on long term storage.

5. Good bioavailability of drugs than from the commercial

tablets or capsules, that dissolved or dispersed in a

water miscible or oily liquids, thus when the capsule

ingested, the drug dispersed as solution or emulsion to

give a drug dispersion of high surface area

52 8/12/2022 Umar Farooq

Preparation of Soft Gelatin Capsules

In a soft gelatin capsule formulation the medicament is in

solution or is dispersed as a fine suspension in either a
hydrophilic vehicle or a hydrophobic base.

Formulation of soft gelatin capsules

There are two main aspects to be considered during the
formulation of soft gelatin capsules:
The composition of the gelatin shell and the composition of
the fill material.

53 8/12/2022 Umar Farooq

 Formulation of the gelatin shell

The composition of the soft capsule shell consists of two

main ingredients: gelatin and a plasticize (e.g. glycerol).

Water is used to form the capsule and it may be desirable or

even necessary to add other additives such as preservatives,

dyes, opacifiers and, rarely, flavours and drugs.

54 8/12/2022 Umar Farooq

 Gelatin
To produce shells with a greater flexibility than hard gelatin
capsules it is necessary to control carefully the viscosity and
strength of the gelatin used in production.

Low viscosity = Thin sheet-Prolong drying

High Viscosity = Thick sheet-Hard-hig sealing tem

The mechanical properties of the gelatin shells are controlled

by choice of gelatin grade and by adjusting the concentration
of plasticizer in the shell.

55 8/12/2022 Umar Farooq

 Plasticizers
The main plasticizer used for soft gelatin capsules is
glycerol.
Sorbitol and propylene glycol in combiatin with glycerol.
The greater the plasticizer content the greater the
flexibility of the shell. (0.3-1.0 parts of dry plasticizer to 1
part of dry gelatin).
Low ratios 0.3-0.5 are used for oily liquid fills,
(0.4-0.6) for oily fills with added surfactant,
(0.6-1.0) for water-miscible fills and chewable capsules.

56 8/12/2022 Umar Farooq

 Water
The demineralized water content of gelatin solution used
to produce a soft gelatin capsule shell depends on the
viscosity of gelatin used (0.7-1.3 parts of water to each
part of dry gelatin), 1: 1 ratio being typical.

Preservatives
Preservatives are added to prevent mould growth in the
gelatin shell. Potassium sorbitate and methyl, ethyl and
propyl hydroxybenzoate (methyl-, ethyl- and
propylparaben) are common additives.
57 8/12/2022 Umar Farooq
 Colours
A wide range of colours can be incorporated into soft
gelatin shells
Water-soluble dyes (synthetic and vegetable), insoluble
inorganic and organic pigments and lakes.

Opacifiers
Titanium dioxide is the most common. It is added in
concentrations of about 0.01-0.5%.

Enteric treatment
Enteric properties can be imparted to soft gelatin shells by
coating with 4%
58
cellulose
8/12/2022
acetate phthalate. Umar Farooq
 Formulation of the capsule contents

Any non-aqueous liquid or powdered solid in suspension

can be filled into soft gelatin capsules.
It is possible to fill soft gelatin capsules with a very wide
range of materials.
Suspensions, pastes, drugs in solution in either oils, self-
emulsifying oils or water-miscible liquids.

59 8/12/2022 Umar Farooq

Limitations for fill materials
Drugs or excipients containing large amounts of water or
other gelatin solvents cannot be incorporated.
It is not recommended to fill emulsions (whether they be o/w
or w/o) since they are unstable and will crack as the water is
lost from the shell in the manufacturing process.
Surfactants may have a deleterious effect on the capsule seal.
Extremes of pH must be avoided. pHs below about 2.5 attack
the gelatin leading to hydrolysis and leakage and pHs above
about 7.5 have a tanning effect on the gelatin, and affecting
the solubility of the shell.
Aldehydes must also be avoided since these have a tanning
action on the 60proteins of the gelatin shell.
8/12/2022 Umar Farooq
Liquid vehicles
Water-immiscible oils or water-miscible liquids.

Water-immiscible oils:
Either volatile or non-volatile oils,
Fixed aromatic vegetable oils,
Aliphatic, aromatic and chlorinated hydrocarbons,
Liquid ethers and esters.

61 8/12/2022 Umar Farooq

Water-miscible liquids (hydrophilic)
Polyols as Polyethylene glycols with low molecular weight
(400-600) since they are liquid at ambient temperatures.
Alcohols as isopropyl alcohol, polyglycerols, triacetin,
glyceryl esters, sorbitan esters, sugar esters and
polyglyceryl esters.
Propylene glycol and glycerol can be used, but the
concentration must be low, (5-10%), in order to prevent
migration into the gelatin and softening of the shell.

62 8/12/2022 Umar Farooq

Suspensions
The particle size of the solid should be reduced to less than
180 µm to pass through the filling head.
Insoluble drugs can be dispersed (with suspending agents
and surfactants) in the above vehicles or combinations of
vehicles.
Suspending agents are added to prevent settling and
maintain homogeneity
• For oily bases (beeswax, paraffin wax, ethylcellulose
and hydrogenated vegetable oil)
• For non-oily bases (solid glycol esters as PEG 4000 and
PEG 6000). 63 8/12/2022 Umar Farooq
Surfactants as polysorbate 80 (Tween 80) are often added
as wetting agent.
Caking of suspensions in soft gelatin capsules can be
avoided by rheological control of the vehicle.

64 8/12/2022 Umar Farooq

Prep./filling of Soft Gelatin Capsules
 A warm sheet of gelatin (plain or colored) is placed on
the bottom plate of the mold.
 The liquid medication is poured on it.
 Then a second sheet of the prepared gelatin is carefully
laid in place on top of the medication, and the top plate
of the mold is put in place.
 The entire mold is then subjected to a press where
pressure is applied to form, fill, and seal the capsules
simultaneously.
 The capsules are then removed and washed with a
solvent harmless to the capsules.
65 8/12/2022 Umar Farooq
ROATRY DIE PROCESS
 Liquid gelatin flowing from an overhead tank is formed
into two continuous ribbons by the rotary die machine
and brought together between twin rotating dies.

 At the same time, metered fill material is injected

between the ribbons at the moment that the dies form
pockets of the gelatin ribbons.
 These pockets of fill-containing gelatin are then sealed
by pressure and heat.
 The soft gelatin capsules may be prepared of single or
two-tone color, the latter resulting from the employment
of two different colored ribbons of gelatin to form the
sides of the capsule.

66 8/12/2022 Umar Farooq

67 8/12/2022 Umar Farooq
68 8/12/2022 Umar Farooq
69 8/12/2022 Umar Farooq
• Capsules are usually packaged in glass or in plastic

containers

• Some container containing packets of a desiccant to

prevent the absorption of excessive moisture by the

capsules.

• Soft capsules have a greater tendency than do hard

capsules to soften and adhere to one another, and they

must be maintained in a cool, dry place.

70 8/12/2022 Umar Farooq

71 8/12/2022 Umar Farooq