Capsules: Part ONE

PHS 2302: Solid Dosage Forms

Pharmaceutics unit-MUK

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Content of Lecture
 Introduction to Capsules
 Capsule shell components:
◦ Gelatin
◦ Plasticisers
◦ Colorants
◦ Preservatives
 Hard gelatin capsules
◦ Manufacture of capsule shells
◦ Capsule sizes
◦ Determination of fill weight
◦ Filling of Capsules
 Diluents, glidants, lubricants, surfactants
◦ Sustained release capsules
◦ Encapsulation Machinery
 Hand-operated
 Semi-automatic
 Automatic
Capsules
 Latin ‘Capsula’ = Small Box
 A capsule is an edible package made from
gelatin and filled with medication to
produce a unit dose
 Mainly oral use
 Hard Capsules
◦ Have a body and a cap which fit one inside the
other
◦ Are produced empty, then filled in a separate
operation
 Soft Capsules
◦ Are manufactured and filled in one operation
 Bothtypes are usually intended to be
swallowed whole
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Gelatin
Has four essential basic properties
1.It is non-toxic
2.It is readily soluble in biological
fluids at body temperature
3.It is a good film-forming material
4.Gelatin films can be prepared easily
without large quantities of heat or
the use of volatile organic solvents.
Gelatin changes from a sol to a gel
at temperatures only a few degrees
above ambient.

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Gelatin
Gelatin is obtained by the partial
hydrolysis of collagen obtained from
the skin, white connective tissue and
bones of animals
Gelatin has a high affinity for water
which may increase the chance of
microbial growth.
Gelatin is insoluble in cold water
Gelatin softens when in contact with
water due to absorption
◦ Can absorb 10 times its own weight
Dissolves rapidly in the stomach
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Properties of Gelatin
Most important properties are
Bloom Strength and Viscosity
Bloom Strength
◦ The load in g required to push a
standard plunger (diameter 12.7 mm) a
set distance (4 mm) into a prepared
gelatin gel (6.66% solution at 10˚C)
◦ Hard capsules use high bloom gelatin
◦ Soft capsules use lower bloom
Viscosity
◦ Is used to control the thickness of
gelatin films or sheets

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Plasticisers
Used in soft capsules to make the
capsule walls more soft and flexible
Soft caps are turgid as they are
manufactured and filled in one operation
◦ The pressure of the contents maintains the
capsule shape
Glycerol is the most frequently used
plasticiser
◦ Others are sorbitol, propylene glycol, sucrose
and acacia
Hard caps very rarely contain
plasticisers

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Colorants
Soluble Dyes
◦ Synthetic
◦ It is possible to produce capsules in any
colour by mixing the dyes
Insoluble Pigments
◦ Titanium dioxide
 Very commonly used
 White colour
 Used as an opacifying agent
◦ Iron oxides
 Black, red and yellow

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Preservatives
Sometimes added in-process to
prevent microbiological
contamination during manufacture
Soft gel capsules sometimes have
antifungal agents added to prevent
growth on surfaces when they are
stored in non-protective packages

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Manufacture of Hard Gelatin
Shells
Pairs of stainless steel pins are dipped into
gelatin solution to make cap and body
When removed from the solution, the
bodies and caps are rotated
◦ Distributes gelatin evenly over the surface
Thendried in dry air, not too much
temperature elevation (to prevent melting)
◦ Overdrying: shells too brittle
◦ Underdrying: shells too sticky
Shells
are then stripped from the pins,
trimmed to the required length, and joined

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Hard Capsules
Size of Capsule Volume in ml

5 0.13

4 0.20

3 0.27

2 0.37

1 0.48

0 0.67

00 0.95

000 1.36

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Determination of Fill
Weight
Capsule fill wt = tapped bulk density of
formulation x capsule
volume

A formulation has a fill weight of 500mg

and a tapped bulk density of 0.80gml-1.
What size capsule is needed?

Capsule vol = 0.5 = 0.63ml

0.8
Size 0 cap = 0.67ml, but 0.04ml would be
unoccupied
Need diluent to fill it
0.04 x 0.8 = 0.032g or 32mg diluent needed
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Filling of Capsules
Formulation must
◦ Be able to be accurately dosed into
capsule shell
◦ Release active contents in a form which
is available to the patient
Formulation is a blend of active
ingredient and adjuvants to aid the
manufacturing process
◦ Diluents
◦ Glidants
◦ Lubricants
◦ Surfactants

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Diluents
Low dose drugs are mixed with free
flowing diluents (e.g. maize starch) to
improve flow
Diluents are not always inert
For readily soluble drugs, choose an
insoluble diluent
◦ e.g. starch
◦ To avoid competition for solution
For insoluble drugs, choose a soluble
diluent
◦ e.g. lactose
◦ To make the mixture more hydrophilic

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 Glidants and Lubricants
 Glidants and lubricants are used to improve
the filling properties of the powder mixture
 Higher dose drugs have less free space in cap
◦ ≤ 5% w/w glidant added
◦ Increases flow by decreasing interparticulate
friction
◦ e.g. colloidal silicon dioxide
 Lubricantsdecrease powder to metal
adhesion and enable dosing devices to
function properly
◦ E.g. magnesium stearate
 Tryto avoid lubricants that make
formulations hydrophobic
◦ Dissolution rate becomes much slower
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 Surfactants (Wetting
Agents)
 Canbe used where hydrophobic compounds
need to be included in the formulation to
improve filling performance
◦ e.g. when magnesium stearate is used as a
lubricant
 Polyol surfactants added at levels of 0.1-0.5%
◦ e.g. sodium lauryl sulphate
 They increase the wetting properties of the
powder bed following release within the G.I.T.
 Also used in densely packed capsules
◦ Dense packing ⇒slower dissolution rate
◦ Surfactant ⇒ increased deaggregation of particles
⇒ increased dissolution rate

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Sustained-Release
Capsules
Some hard capsules contain sustained
release drug pellets
These drug pellets are coated with
different thicknesses of coatings or
materials
◦ The variation in the thickness of the
coating will allow body fluids to penetrate
the coating and dissolve the drug at
different rates
◦ A sustained-release effect will occur
Alternativelythe gelatin shell can be
coated with a modified release coat
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Manufacture of Hard
Capsules
In large scale industrial
manufacturing of capsules, the
amount of formula prepared fills
thousands of capsules.
In the industrial setting, machines
can make over 30,000 capsules/hour.
In the community or hospital setting,
the amount of formula prepared fills
anything from a few to hundreds of
capsules.

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Encapsulation Machinery
Commonly referred to as a
capsule filler
Three types:
◦ Hand-operated
◦ Semi-automatic
◦ Automatic
 Continuous
 Intermittent

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Hand-operated
Encapsulator
Requires the operator to organize
the capsules in the correct
position, separate the cap from
the body, and fill & close the caps
◦ (basically the hand-operated capsule
filler is a holder for the capsule
body).
See page 212 of Ansel’s
Pharmaceutical Dosage forms for
illustration
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Dependent Dosing Method
 Lower half of cap placed into slots within a
revolving turntable
 Turntable is rotated under a hopper that
contains the powder formulation
◦ As a result, powder falls into capsule
 Flow of powder through hopper and
homogeneity of powder mix maintained by
an auger
 At the end of operation, the two casule
halves are brought together
 Mass of powder is dependent upon the
length of time the hopper spends above the
capsule
◦ Dependent on speed
 Capsules removed from turntable
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Diagram of Semi-Automatic
Encapsulator
Independent Dosing
Method
Involves the transfer of a plug of
powder into the capsule
A spring-loaded piston is depressed
into a powder bed
◦ This forms a powder plug in the tube
◦ Piston settings control volume of powder
plug
Tube containing the powder plug is
then elevated out of powder bed,
rotated and located above the lower
half of capsule
Plug of powder dispensed into
capsule by depression of piston
Semi-Automatic
Encapsulator
Requires the operator to move
rings (capsule holder rings) from
the rectifier to the filling and
closing stations
Allows for production of up to
25,000 capsules per hour

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Automatic Encapsulator
 Can produce up to 90 000 capsules per
hour
 Intermittent motion machine is divided
into segments. Each segment indexes
from each machine function
◦ Rectify
◦ Fill
◦ Tamp
◦ Close
◦ Eject
 Continuous
motion machine is
comparable to a rotary tablet press
◦ Rotation is continuous and does not start
and stop
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