SOFT GELATIN CAPSULES

Pharm. D 4th SEMESTER

 DEFINITION
• Soft gelatin capsules consist of a hermetically sealed
outer shell of gelatin that encloses a medicament in the
unit dosage. Soft gelatin capsules are a completely sealed
dosage form and cannot be opened without destroying
the capsules.
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• Soft gelatin capsules are generally filled with liquids, where the drug is dissolved
or dispersed in a solvent however, they are used to encapsulate and hermetically
seal liquids, suspensions, pasty materials, dry powders, and even preformed
tablets.
• Soft gelatin capsules are pharmaceutically elegant and are easily swallowed.
• Drugs that are commercially prepared in soft capsules include cyclosporine,
declomycin, Ranitidine HCl, digoxin, vitamin A, vitamin E, and chloral hydrate
 COMPONENTS OF GELATIN SHELL

1. Gelatin
Most commonly, the gelatin is alkali- (or base-) processed (type B)
gelatin and it normally constitutes 40% of the wet molten gel mass. Type
A acid-processed gelatin can also be used
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2. Plasticizers
Plasticizers are used to make the softgel shell elastic and pliable.
They usually account for 20–30% of the wet gel formulation.
The most common plasticizer used in softgels is glycerol, although
sorbitol and propylene glycol are also frequently used, often in
combination with glycerol.
The gelatin is plasticized by the addition of these material which gives the
shell its characteristic flexibility
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3. Water
The other essential component of the softgel shell is water. Water usually
accounts for 30–40% of the wet gel formulation and its presence is important
to ensure proper processing during gel preparation and softgel encapsulation.
Following encapsulation, excess water is removed from the softgels through
controlled drying.
In dry softgels, the equilibrium water content is typically in the range of 5–
8% w/w which represents the proportion of water that is bound to the gelatin
in the softgel shell.
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4. Colourants/opacifiers
• Colourants (soluble dyes or insoluble pigments or lakes) and opacifiers
are typically used at low concentrations in the wet gel formulation.
• An opacifier, usually titanium dioxide, may be added to produce an
opaque shell when the fill formulation is a suspension or to prevent
photodegradation of light-sensitive fill ingredients.
• Titanium dioxide can either be used alone to produce a white opaque
shell, or in combination with pigments to produce a coloured opaque
shell.
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• Soft gelatin capsules may be oblong, oval, or round.
• They may be single colored or two toned and may be imprinted with
identifying markings.
• As with hard gelatin capsules, they may be prepared with opaquants to
reduce transparency and render characteristic features to the capsule
shell.
• The shell may be transparent or opaque and can be coloured and
flavoured if desired.
• The softgel can be coated with enteric-resistant or delayed-release
coating materials.
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• Although virtually any shape of softgel can be made, oval or oblong shapes are
usually selected for oral administration. Softgels can be formulated and
manufactured to produce a number of different drug delivery systems:

1. Orally administered softgels containing solutions or suspensions that release

their contents in the stomach in an easy-to-swallow, convenient unit dose form
2. Chewable softgels, where a highly flavoured shell is chewed to release the
drug liquid fill matrix. The drug(s) may be present in both the shell and fill matrix
3. Suckable softgels, which consist of a gelatin shell containing the flavoured
medicament to be sucked and a liquid matrix or just air inside the capsule
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4. Twist-off softgels, which are designed with a tag to be twisted or

snipped off, thereby allowing access to the fill material. This type of
softgel can be used for unit dosing of topical medication, inhalations
or for oral dosing of a paediatric product
5. Meltable softgels designed for use as patient friendly pessaries or
suppositories.
 PREPARATION OF SOFT GELATIN CAPSULES

• Before the encapsulation process takes place, two sub-processes are often carried
out simultaneously, yielding the two components of a softgel. These are

(a) the gel mass which will provide the softgel shell and
(b) the fill matrix for the softgel contents
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• The gel mass is prepared by dissolving the gelatin in water at approximately 80°C
under vacuum, followed by the addition of the plasticizer, for example, glycerol.
• Once the gelatin is fully dissolved then other components such as colours, opacifer
and flavours may be added. The hot gel mass is then supplied to the encapsulation
machine through heated transfer pipes by a casting method that forms two separate
gelatin ribbons, each with a width of approximately 150 mm.
• The thickness of the gel ribbons is checked regularly during the manufacturing
process
• Each gel ribbon provides one half of the softgel. It is possible to make bicoloured
softgels using gel ribbons of two different colours
PREPARATION OF SOFT GELATIN CAPSULES

• Soft gelatin capsule may be prepared by

1. Plate process
2. Rotary die process
3. Reciprocating die process
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1. Plate Method
• By the plate process, a warm sheet of plain or colored gelatin is placed on the
bottom plate of the mold, and the medication-containing liquid is evenly
poured on it.
• Then a second sheet of gelatin is carefully placed on top of the medication,
and the top plate of the mold is put into place.
• Each gel ribbon provides one half of the softgel. It is possible to make
bicoloured softgels using gel ribbons of two different colours
• Pressure is then applied to the mold to form, fill, and seal the capsules
simultaneously.
• The capsules are removed and washed with a solvent harmless to the capsules.
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2. Rotary Die Process

• Most soft gelatin capsules are prepared by the rotary die process, a
method developed in 1933 by Robert P. Scherer
• By this method, 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 and an injection wedge.
• Accurate filling under pressure and sealing of the capsule wall occur as
dual and coincident operations; each is delicately timed against the other
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• At the same time, metered fill material is injected between the ribbons precisely at
the moment that the dies form pockets of the gelatin ribbons.
• These pockets of fill containing gelatin are sealed by pressure and heat and then
separated from the ribbon.
• Use of ribbons of two different colors results in bicolored capsules
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3. Reciprocating Die Process

• This process is similar to the rotary process in that ribbons of gelatin are
formed and used to encapsulate the fill, but it differs in the actual
encapsulating process.
• The gelatin ribbons are fed between a set of vertical dies that continually
open and close to form rows of pockets in the gelatin ribbons.
• These pockets are filled with the medication and are sealed, shaped, and
cut out of the film as they progress through the machinery.
• As the capsules are cut from the ribbons, they fall into refrigerated tanks
that prevent the capsules from adhering to one another.
USES/APPLICATIONS OF SOFT GELATIN CAPSULES

1. Improved drug absorption

2. Increased bioavailability
3. Patient compliance and consumer preference
4. Safety for potent and cytotoxic drugs
5. Dose uniformity of low-dose drugs
6. Product stability
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• Improved Drug Absorption
For poorly water-soluble drugs, ideally the dosage form would present the
drug to the gastrointestinal tract in solution form, from which the drug can
be rapidly absorbed.
This can be achieved using a drug-solution matrix in a softgel formulation
and such formulations can provide faster absorption than from other solid
oral dosage forms, such as compressed tablets
With the solution-softgel approach, the shell ruptures within minutes to
release the drug solution, which can be in a hydrophilic or highly
dispersing vehicle that aids the rate of drug absorption
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• Increased bioavailability
As well as increasing the rate of absorption, softgels may improve the extent of
absorption
An example of such a product is the protease inhibitor saquinavir, which was
formulated as a solution-softgel product
The solution-softgel formulation provided around three times greater bioavailability
than a saquinavir hard-shell capsule formulation
• In some cases a drug may be solubilized in vehicles that are capable of
spontaneously dispersing into an emulsion on contact with gastrointestinal fluid.
This is known as a self-emulsifying drug delivery system (SEDDS)
• This can increase bioavailability compared to formulations in which the drug is
dosed in the solid state
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• Patient compliance and consumer preference

A number of self-medicating consumer preference studies have been
carried out to gauge the user’s perception of softgels relative to hard-shell
capsules and tablets.
The results of the studies showed that consumers expressed their
preference for softgels in terms of
(a) ease of swallowing,
(b) absence of taste and
(c) convenience in use
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• Safety for potent and cytotoxic drugs

Dissolving potent drugs in a liquid vehicle reduces the risk of operator
exposure to dusts that is present with tablet and hard gelatin capsule–
manufacturing operations.
The dust or airborne particles produced during handling can be a cause of
concern for the manufacture of highly potent or cytotoxic compounds
because of safety considerations for the operator and environment.
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• Dose uniformity of low-dose drugs

Because soft gelatin capsules are filled with liquids or suspensions,
excellent content uniformity can be achieved with even the most potent of
drugs.
The accuracy of the filling mechanism enables the dose to be filled to a
tolerance of 1% for solutions and 3% for pastes.
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• Product Stability
If a drug is subject to oxidative or hydrolytic degradation, the
preparation of a liquid-filled softgel may prove beneficial. The liquid
is prepared and encapsulated in a protective nitrogen atmosphere and
the subsequent dried shell has very low oxygen permeability.
Varying the level of glycerol in the shell formulation will alter the
permeability of the shell to oxygen.
The filling process can be performed under nitrogen, so by
appropriate selection of shell composition, this technology can
provide excellent protection for oxygen-sensitive drugs
INSPECTING, COUNTING, PACKAGING AND
STORING CAPSULES
• Capsules produced on a small or a large scale should be uniform in
appearance. Visual or electronic inspection should be undertaken to
detect any flaws in the integrity and appearance of the capsules.
Defective capsules should be rejected
• In the pharmacy, capsules may be counted manually or by
automated equipment. Specially designed trays are used for counting
small numbers of solid dosage units.
• In some community and hospital pharmacies, small automated counting
and filling machines may be used
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• On the industrial scale, solid dosage forms are counted by large

automated pieces of equipment that count and transfer the desired
number of dosage units into bulk containers. The containers are then
mechanically capped, inspected visually or electronically, labeled, and
inspected once more. Some filled containers are then placed in outer
packaging cartons
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• Packaging> Capsules are packaged in glass or in plastic

containers, some containing packets of a desiccant to prevent
absorption of excessive moisture.
• Typical small scale strip packaging equipment and commercial
unit-dose packages of capsules and tablets are available

• Storing> Capsules should be stored in tightly capped

containers in a cool, dry place.