Soft Gelatin Capsules

Technology
Murugesan. L
 INDEX
1. Definition
2. Advantages
3. Disadvantages
4. Components of Soft gelatin Capsules
5. Composition of Shell
6. Composition of Fill
7. Manufacturing Process
8. Encapsulation
9. Physicochemical problems in soft gel capsules
Definition:
Soft gelatin capsules are single-
unit solid dosage form, consisting
of a liquid or suspension or
solutions fill enveloped by a one-
piece hermetically sealed elastic
outer shell.
Advantages:
 Versatile size, shapes and elegance
 Easy to swallow, no taste, unit dose
delivery, tamper-proof
 Content uniformity
 Enhanced bioavailability
 Encapsulation of volatile substances
 Patient compliance
 Enteric resistant capsules
 Reduced gastric irritation
Disadvantages:
 Soft gelatin capsules are expensive
dosage form
 There is more intimate contact between
liquid fill and shell than in case of hard
gelatin capsules. This increases the
possibility of shell-fill interaction
 Drugs can migrate from fill into shell.
 If the fill contains hydrophilic substances,
it can attract water from the shell during
drying
 Limited choices of excipients /carriers
compatible with the gelatin
 Components of Soft Gels
Soft gel consists of two major parts:
1. Shell
2. Fill
Shell – Outer core or Gelatin matrix consists of
gelatin, plasticizer, solvent and optional
ingredients such as opacifiers and colorants
Fill – Inner material which is of two types as
follows:
 Solution Fills: Active dissolved in a carrier
 Suspension Fills: Active dispersed in a carrier
 Compositions of Shell

 Gelatin
 Plasticizer
 Solvent
 Optional Ingredients
• Colors
• Opacifiers
A typical soft capsule shell formula would be:

Gelatin 40 – 45%

Plasticizer 15 - 25%
Water QS to 100%
 Gelatin
TYPES OF GELATIN
Depending on the source of gelatin, it is divided into
different types like,
 Type A gelatin obtained by acid treatment of pig skin
 Type B gelatin obtained by alkali treatment of cattle skin
and bones
 Type C gelatin obtained from calf skin
 Type AB gelatin obtained by the acid treatment of bone
gelatin
 Type S gelatin obtained from the skull
 Gelatin obtained from chicken bones
 Fish skin gelatin
 Gelatin obtained from vegetable sources
Physicochemical Properties of Gelatin

Gelatin can be obtained in different grades

which will be termed as Bloom strength like
120 – 200.
Gelatin when converted to Gelatin solution, it is
more susceptible for Microbial growth hence
proper care to be taken while usage of the
gelatin solution
 Plasticizer
Plasticizer is an important part of soft
gelatin capsule shell formulation.
Plasticizer will give Tensile strength to the
capsule. Without plasticizer the gelatin
shell will be too hard and brittle.

Common plasticizers used in the gelatin

shell include Glycerin, Sorbitol, Sorbitol
special, Anidrisorb, Propylene glycol and
PEG 400
 Solvents & Optional Ingredients
 Solvents:
Mainly water is used as solvent
 Colors:
Colors are used in the soft gelatin
capsules shell for product elegance and for
protection from light. Water soluble colors
(supra) and water insoluble colors (lake) or iron
oxides
 Opacifiers:
Titanium dioxide is used as the opacifier
 Compositions of Fill
Solution Fills:
 Oils such as soybean oil and Miglyol 812
(neutral oil, triglycerides of medium chain
fatty acids)
 Polyethylene Glycols: especially PEG 400
-600
 Other solvents: Any other solvent which
doesn't degrade or solubilize the gelatin
shell, i.e., dimethyl isosorbide, surfactants,
diethylene glycol monoethly ether
 Compositions of Fill
Suspension Fills:
Suspension fills mainly consists of active and suitable
carriers
Carriers
Oily mixtures: Soybean Oil with beeswax (1-5% w/w),
hydrogenated vegetable oil(3 – 10%) and lecithin (1-
3% w/w). The lecithin improves material flow, and
imparts some lubrication during filling.
Hydrophilic mixtures: Polyethylene glycol, PEG 800 -6000
or mixtures of the above. Heat up to 35ºC to make
fluid enough for filling. For the formulation of semi-
solid solutions and suspensions, the low molecular
weight polyethylene glycols (PEG 300–600) are
mixed with high molecular weight solid polyethylene
glycols, such as PEG 4000–10000, to increase the
viscosity
 Compositions of Fill
Optional Ingredients:
 Water or alcohol: up to 10% w/w, if needed for
solubility
 Glycerin: 1 to 4% w/w to retard the migration of
the glycerin out of the shell into the fill
 Polyvinylpyrrolidone: Up to 10% w/w used in
combination with PEG, can increase drug
solubility, and also improve stability by inhibiting
drug recrystallization
 Surfactant: Sorbitan derivatives such as
polysorbate 80 or lecithin
 Antioxidants: Antioxidants are usually added to
stabilize oxygen-sensitive drugs
 Manufacturing Processes
Gelatin paste preparation:
 Hot Process : In this process, plasticizers and water are
mixed together and charged into a melter. This mixture is
heated to 80°C to 85°C and gelatin is charged into the
melter with continuous mixing. The gelatin paste formed
is subjected to vacuum and application of vacuum is
continued till gelatin paste is free of air bubbles.

 Cold Process : The preparation of suitable gelatin mass

involves the blending of chilled water (7°C) water,
plasticizers and gelatin using immersion type mixers. .
The mixture is then blended until a light fluffy
consistency is obtained. The mixture is then transferred
into a melter.
Fill Preparation:
 Solution
 Suspension

Main factor to be considered during fill preparation is Base Adsorption.

Base adsorption is expressed as the number of grams of liquid base
required to produce a capsulable mixture when mixed with one gram
of solid. In the determination of base adsorption the solids must be
completely wetted by liquid base.
Weight of base
------------------ = Weight adsorption
Weight of the solid

Solution: Usually a solution is more easy to be capsulated and exhibits a

better uniformity, stability, and biopharmaceutical properties than a
suspension.
Those liquids that are both water miscible and volatile cannot be a
major content of capsule since they migrate into the shell and volatilize
from the surface. (Water, ethyl alcohol and emulsions).
Suspension: Solids that are not sufficiently soluble
in liquids or in combination of liquids are
encapsulated as suspensions. Such material
should be #80 mesh or finer in particle size, to
avoid the blockage of injection segment.
Choice of suspending medium are directed
towards the producing the smallest size of
capsules with maximum physical and ingredient
stability and therapeutic efficacy.
All liquids, solutions and suspensions for
encapsulation should be homogenous, air free
and preferably should flow by gravity at Room
Temperature.
ENCAPSULATION
ENCAPSULATION
 ENCAPSULATION
Encapsulation machine parts:
 Gelatin tank
 Product holding tank/hopper
 Spreader box
 Cooling drum
 Oil rolls
 Segment/Injection wedge
 Leads/Spider tubes
 Die roll
 Chute
 Conveyor belt
 Tumble drier
 Tunnel drier
Encapsulation process:
 Heated gelatin tanks are suspended above the
encapsulation machine from which gelatin flows
by gravity or gelatin is pumped from gelatin
tanks to two spreader boxes on both sides of the
encapsulation machine.
 The heated gelatin mass is then metered into an
air cooled (8-15°C) drums where the gelatin
cools and a ribbon is formed. The cast ribbon
lifts off the casting drum and pass through a
mineral oil lubricating bath which deposits a film
of oil on either sides of the die rolls.
 The ribbon moves forward up and over the feed
rollers and fed between the injection wedge and
rotary dies of encapsulation machine.
 Medicine receiver delivers the fluid for
encapsulation through a hopper or manifold
mechanism into the positive displacement filling
pump. The medicine mix is metered by pump
action through a series of leads through the
injection wedge.
 Finished soft gelatin capsules formed sealed
and ejected through by the action of rotating
dies are dropped into a conveyer.
 The conveyer moves the capsules into tumble
drier.
 The final drying phase for the soft gelatin
capsules are accomplished in drying tunnels.
 The stacks of drying trays are inserted into
tunnels in which controlled temperature (15-
20°C ) and low humidity (20% to 30% RH) air
continuously circulates.
 After drying the gelatin shell contains 6% to 10%
moisture.
 Capsules are then subjected wiping to remove
adhering lubricating oils and other impurities.
 In this process, the capsules are wiped with a
wiping cloth after moistened with
tetrachloroethylene or isopropyl alcohol.
 The capsules are sent for inspection for physical
defects like leakers, color migration; soft spots
are detected and removed in this process.
Soft gel Shapes and Sizes
Soft gel Shapes and Sizes
Soft gel Shapes and Sizes
 PHYSICOCHEMICAL PROBLEMS OF SOFT
GELATIN CAPSULES

 Blooming: Blooming is the visual

crystallization of a solid in the shell
Corrective action: Lowering the
thermodynamic activity of the crystallizing
material.
 Browning: This is the darkening of the
shell due to the Millard reaction between
proteins and polysaccharides.
Corrective action: Proper gelatin
selection, color selection, and rapid drying.
 Leakers: This is the seepage of fill material through the shell.

Polar leakers
Seam leakers
End leakers
Air bubbles in the shell
Use of low bloom paste
Corrective action:
 In case of polar leakers reformulation of fill is required to
correct the incompatibility of fill.
 Incase of seam leakers shell needs rework.
 When the leakers are because of air bubble entrapment,
proper de-aeration steps are to be taken.
 Gelatin paste should be stored in cold conditions, if not
going to be consumed within a day to retain bloom.
 De-shapes:
This is due to the
 Non uniform thickness of the gelatin ribbon
 Presence of air bubbles in the gelatin paste
 Non-uniform temperature during drying
Corrective action:
 Proper adjustment of ribbon thickness
 Ensuring paste is free from air bubbles
 Uniform drying temperature during drying
 Separation of fill: This is seen in suspension
type fill
Corrective action: Addition of thickeners or
increasing the viscosity of the fill or increasing
the density of the vehicle.
 Segment blockage: Due to the increased particle size
or due to the tacky nature of the solid materials of the fill
materials
Corrective action:
 Proper reduction of size of particles in the
suspensions
 avoid formation of lumps in the fill preparation.
 Color transfer/bleeding/migration:
Usually seen in double colored soft gelatin capsules
Corrective action:
 Selection of proper gel formula, color system and
proper drying condition
 Weight variation of soft gelatin capsules can be caused by
various reasons:

 Presence of air bubbles in the fill

 Improper setting of wedge
 Improper setting of piston pump

Corrective action
 Proper de aeration of fill by applying vacuum.
 If the weight variation is because of air bubble entrapment,
the point of entrapment should be identified and necessary
action should be taken.
 Proper setting of the wedge, then the washers
 Proper setting of piston pump
 If the setting of the plungers are not arranged uniformly, there
is a chance of getting irregular weights. The corrective action
of this is the proper setting of plungers.
Migrations of compounds from fill to shell :
The rate of drug migration is greater in formulations
containing PEG 400 than PEG 600.
This is due to
 water soluble ionized form of the drug
 The rate of drug migration increases exponentially
with an increase in the concentration of drug in the
fill.
 The migration of the drug from the shell into the fill
occurs because the ionized species of the drug
molecule is soluble in the shell formulation.
Corrective action:
 Reformulation of the fill
Thank You