CAPS

ULES

Definition
Capsules

are solid dosage form in

which the drug substance is enclosed
in water soluble shell or envelope.

Capsule

gelatin.

shell is mostly made up of

US Pharmacopeia (USP 24): It denes capsules

as solid dosage forms in which the active
ingredients are sealed in a hard or soft
container or shell.
The European Pharmacopoeia (Eur. Ph.)
describes capsules as follows: 'Capsules are
solid preparations with hard or soft shells of
various shapes and capacities, usually
containing a single dose of active ingredient.
They are intended for oral administration.'

History

The capsule is one of the oldest dosage forms

in pharmaceutical history, known to the
ancient Egyptians.
The earliest European reference is contained
in a travel account of 1730 which mentions
the pharmacist de Pauli from Vienna, who
produced oval-shaped capsules in the hope
of covering up the unpleasant taste of the
pure turpentine he prescribed for people
suffering from gout.

A further 100 years were to pass before the

rst gelatin capsule appeared.
The rst patent for such a product was
granted in 1834 to the pharmacist Joseph
Grard Auguste Dublanc and the pharmacy
student Franois Achille Barnab Moths.
Moths, who ended his collaboration with
Dublanc in 1837, continued to work on
improving the gelatin capsule and to take out
patents for the manufacture and use of
capsules.

Moths' invention was so successful that, by the

following year, capsules were being produced in
many different parts of the world.
Eventually, this resulted in several more patents for
gelatin capsules being taken out by others, not
least to circumvent those held by Moths.
The Frenchman Jules Csar Lehuby was successful
in this strategy and, in 1846, was granted a patent
for his 'medicine coverings', which formed the
basis of his future inventions.

 He

was also the first to suggest two-piece

capsules, which he produced by dipping
silver-coated metal pins into a gelatin
solution and then drying them.
It was in 1931 that Arthur Colton, on
behalf of Parke, Davis & Co., succeeded
in designing a machine which
simultaneously manufactured both bodies
and caps and tted them together to
form a hard gelatin capsule

Advantages

Drugs with unpleasant taste and odour can be

administered.
Drugs which cannot be compressed can be given in
capsule form.
Prevention of drug by gastric pH or enzymes.
Oily medicaments can be administered.
Economical, easy to handle and carry and attractive in
appearance.
Therapeutically inert - made from gelatin.
Increased bioavailability.

Disadvantages

Concentrated preparation which needs previous dilution

may lead to irritation.

Not suitable for extremely soluble materials sudden

release may cause stomach irritation.
Efflorescent (softens the capsule) and hygroscopic drugs
(absorbs water and makes capsule shell brittle) cannot be
filled.

Types of capsule

Hard Gelatin
capsule (two
piece).

Soft Gelatin
capsule (one
piece).

Raw Materials - Gelatin

Capsules primarily manufactured by gelatin.

Other materials HPMC and starch.

Gelatin - Heterogeneous product derived by irreversible

hydrolytic extraction of treated animal collagen.
Common sources of collagen animal skin, sinews
and/or bovine bones.

Raw Materials - Gelatin

Exhibits excellent physicochemical and biological
properties.
Gelatin from bovine source Transmission of bovine
spongiform encephalopathy (BSE)
Used from countries where low incidences of BSE is
there.
Marinecaps - fish gelatin.
Fish gelatin made from non-ruminant material - do not
pose the risk of BSE
Can readily converted from sol (mobile liquid) to gel
form (rigid).

Gelatin Manufacturing
Type A

Type B
Acid treated.

Alkali treated

Pig Skin.

Demineralised bones.

HCl, H2SO4, HSO3 or H3PO4

Calcium Hydroxide.

Immersed for 1 day.

Immersed for1-3 months.

Extraction through hot water.

Extraction through hot water.

Solution cool to form gel.

Solution cool to form gel.

Evaporation of water dried gelatin.

Evaporation of water dried gelatin.

Isoelectric point between 7 to 9.

Isoelectric point between 4.7 to

5.3

Bone Gelatin
Tough and firm
film.
Tends to be
hazy and brittle.

Pork skin
Gelatin
Plasticity and
clarity.
Reducing haze
or cloudiness.

Blend of bone &

pork skin
Gelatin
High gel
strength.
Normally used
for hard capsule
production.

Physicochemical Properties of Gelatin

Bloom
Strength

Measure of gel rigidity.

Weight (in grams) required to depress a
plunger (of defined diameter, 12.7mm) to a
defined depth (4mm) within an aged gelatin
solution (6.66% w/w in water).
Hard Gelatin 250-280.
Soft Gelatin 150-200.

Viscosity

Controls thickness of film or sheets.

Measured on standard 6.66% w/w solution at
60C in a capillary.
Range: 30-60 millipoise.

Soluble in biological fluids at room temp. (Note:

Gelatin Capsules do not dissolve but swell when
immersed in an aqueous solution <30C.
Excellent mechanical properties exhibiting good film
and hence capsule forming properties.
Excellent rheological properties at elevated temp.
[Sol (mobile liquid) at 50C good for dip processing.]

Undergoes sol-gel transition at relatively low temp.

Other Raw Materials

Diluents

Binders

Disintegrants

Lubricants

Plasticizers

Colorants

Wetting
Agents

Preservatives

To prevent brittleness plasticsers are

added.

Walls of hard gelatin capsule are firm

and rigid.
Whereas walls of soft gelatin capsule are
more soft and flexible.
So soft gelatin contains large proportion
of plasticiser.

Eg: Glycerol, sorbitol, propylene glycol,

sucrose and acacia(optional)

Glycerol/Gelatin Ratio

Application

0.35:1

Oral capsules with oil films

where final capsule should be
hard.

0.46:1

Oral capsules with oil films

where shell requires to be more
elastic.

0.55-0.65:1

Capsules containing oil with

added surfactant or products
with hydrophilic liquid fills.

0.76:1

Oral capsule where a chewable

shell is required.

Important role in identifying the product

Improve the patient compliance.
May be included in heated gelatin.
Two types soluble synthetic (coal tar) and
insoluble pigments (titanium dioxide & iron
oxides)
Titanium dioxide white opacifying agent &
provides protection against light or to conceal the
contents.
White - analgesia; lavender - hallucinogenic
effects; orange or yellow - stimulants and
antidepressants.
FDC approved colours or approved by legislation
of that particular country.

Sodium Lauryl Sulphate.(< 0.15%

w/w)
Increase the wetting properties of
capsule shell.
In turn enhance the dissolution
properties of formulation.
May be included in heated gelatin.
Enhance the wetting of gelatin
solution on metal pins during
manufacturing process.

Sometimes added to prevent

microbial contamination.

Usually antibacterial agents

are used but soft gelatin
capsules contain antifungal
agents also.

Usually parabens are used.

Manufacturing of Hard Capsule Shells Dip-Coating

Method

Collection of
gelatin from
animal source

Mixing with hot

water

Transfer to ss
feed tanks

Add excipients

Stripping

Drying

Rotation

Dipping

Trimming

Joining

Sorting

Printing

1. Once raw materials have been

received and released by Quality
Control, the gelatin and hot
demineralized water are mixed
under vacuum in Stainless Steel
Gelatin Melting System.

2. After aging in stainless

steel receiving tanks, the
gelatin solution is transferred
to stainless steel feed tanks.

3.Dyes, opacifants, and any needed water are added to the

gelatin in the feed tanks to complete the gelatin preparation
procedure. The feed tanks are then used to gravity-feed gelatin
into the Capsule Machine.

4. Dipping

From the feed tank, the gelatin is

gravity fed to Dipper section.
Pairs of the stainless steel pins
are dipped into the dipping
solution to simultaneously form
the caps and bodies.
The pins are at ambient
temperature;
whereas
the
dipping solution is maintained at
a temperature of about 500C in a
heated, jacketed dipping pan.
The length of time to cast the
film has been reported to be
about 12 sec.

5. Rotation

After dipping, pins

are
elevated
and
rotated 2-3 times until
they
are
facing
upward.
This rotation helps to
distribute the gelatin
over
the
pins
uniformly and to
avoid the formation of
a bead at the capsule
ends.
Pin Bars rise to the
upper deck allowing
the cap and body to

6. Drying

The Pin Bars pass

through the upper
and lower kilns of
Capsule
Machine
Drying System.
Here gently moving
air which is precisely
controlled
for
volume, temperature,
and
humidity,
removes the exact
amount of moisture
from the capsule
halves.

7. Stripping
Once

drying
is
complete, the Pin Bars
enter the Table section
which positions the
capsule halves for
stripping from the Pins
in
the
Automatic
section.
A

series of bronze
jaws strip the cap and
body portions of the
capsules from the pins.

8. Trimming

The stripped cap and

body portions are
delivered to collects in
which they are firmly
held.
As the collects rotate,
knives are brought
against the shells to
trim them to the
required length.
The cap and body
lengths are precisely
trimmed to a 0.15
mm tolerance.

9. Joining
(Sealing)
The

cap

and body
portions
are
aligned
concentrically in channels
and the two portions are
slowly pushed together.

Finished

capsules are
pushed onto a conveyer
belt which carries them out
to a container.

SEALING

Sealing

Mechanical
sealing

Gelatin Band
sealing

Hydroalcoholic
solvent seal

Mechanical Sealing (KAPSEAL Technology)

Self locking is made by forming indentations or grooves on the inside
portion of the cap and body portions.

Positive interlock is created between the cap and body portions.

Indentations formed further down of the cap provide a pre-lock that keeps
the empty capsules joined during shipping and handling

Yet allows ready separation for filling.

Eg: Coni Snap.

Gelatin Band Sealing

Dilute solution of
the
gelatin
is
applied to the centre
of
the
capsule
(between the two
halves) which, once
dried, produces a
hermatic seal

Hydro alcoholic Solvent Seal

A

hydro alcoholic solution

(1:1
water/ethanol)
is
applied to the centre of the
capsules (between the two
halves).
This softens the capsule
and following heating to
45 C the interface fuses to
produce a seal.
Setting & hardening
overnight at room temp.
Larger size of seal area as
compared
to
banding
process.
Robust
& impervious

The

entire cycle lasts

approximately for 45 minutes.
Processing
parameters
throughout the production
process. :
1. Humidity
2. Temperature at drying.
3. Gelatin viscosity.
4. Speed of rotation.
Capsule quality is monitored
throughout the production
process
including
size,
moisture content, single wall
thickness, and colour.

10. Sorting
During sorting, the
capsules passing on
a lighted moving
conveyor
are
examined visually
by inspectors.
Defects
are
generally classified
according to their
nature and potential
to cause problems
in use.

11. Printing
In general, capsules are printed
before filling.
Empty capsules capsules can be
handled faster than filled capsules.
If there is any damage to capsule
during
printing
no
active
ingredients would be involved.
Print either axially along the
length of capsules or radially
along the circumference.
Offset rotary presses having
throughput capabilities as high as
three-quarter million capsules per
hour.

Circular

oriented, twocolor printing of the

capsule.
It helps retain brand
identity right until it
reaches the customer.

Brandshield

Brandshield 4c Capsules
Hard

capsules that feature fourcolor circular oriented printing. This

printing technique allows you to
differentiate your brand and is an
effective anti-counterfeit measure.
Imprint your brand logo, brand
name and graphics right on the
capsule, providing exceptional brand
awareness.
Allows you to print two unique
colors on the cap and on two colors
on the body of the capsules.
These capsules offer counterfeit
security right up to the end user.

45

08 June 2009

SIZE & SHAPE:

Empty gelatin capsules are manufactured in eight sizes, ranging
from 000 to 5.
Tapped Bulk Density X Capsule Volume = Capsule Fill Weight
Size

Volume (cm3)

Fill weight(g) at 0.8

g/cm3 powder density

000

1.37

1.096

00

0.95

0.760

0.68

0.544

0.50

0.400

0.37

0.296

0.30

0.240

0.21

0.13

SRTM University, NandedDept. of

Pharmaceutics

0.168

0.104

 The largest size normally acceptable to patient is a No: 0.

Three larger size are available for veterinary use: 10, 11, and
12 having capacities of about 30, 15, and 7.5 g, respectively.
The standard shape of capsules is traditional symmetrical
Oblong shaped.
Some manufactures have employed distinctive shapes.
e.g. Lillys pulvule tapers to a bluntly pointed end.
Smith Kline Beachams spansule capsules taper at
both the cap and body ends.

STORAGE
Equilibrium

moisture
content 13-16%
Critical to maintain the
physical properties of the
shell.
Best to avoid extremes
of temperatures.
Maintain
relative
humidity of 40-60%
Desicant materials are
used. Eg: Dried silica,
clay
and
activated
carbon.

More than
16% - Soft
& Sticky

Less than
13% Brittle and
Fragile

Vegetarian Capsule Need

Animal-free products - driven by personal, cultural or
religious restrictions, or simply a preference not to
consume animal based products.

These consumers are concerned with general good

health and well-being, as well as driven by health
concerns such as heart disease, breast cancer, high
cholesterol and weight control
they are moved by ethical considerations, citing the
environment and/or animal welfare.