CAPSULES

Pharmaceutics 2

Dr. Kabara

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CAPSULES
These are the solid dosage forms of medicaments in which the drug is enclosed
in a practically tasteless hard or soft container /shell made up of a suitable form
of gelatin.
It’s an edible package made from gelatin and is filled with medicines to produce
a unit oral dosage form.

Types of capsules
There are two types.
1. Hard capsules ‘two piece’ – They have two pieces in the form of cylinders
closed at one end. The shorter piece ‘cap’ fits over the open end of the longer
piece ‘body.’ Hard capsules are used for filling solid substances.

2. Soft capsules – “One Piece” – They are used for filling liquids and semi
solids.
Some capsules are administered through the rectum or vagina and may be better
than suppositories.

Advantages of Capsules
1. They are tasteless, colourless and can be easily administered.
2. They are elegant or attractive in appearance.
3. Drugs with unpleasant colour or taste can be enclosed in a tasteless shell.
4. They can be filled quickly and conveniently.
5. They physicians can change the dose and the combination of drugs to suit
individual patients. This is an advantage over tablets.
6. They are economical.
7. They are easy to handle and carry

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Disadvantages
1. Hygroscopic drugs are unsuitable in capsules as they absorb the water
present in capsules making the shell brittle hence it crumbles into pieces.
2. Concentrated solutions that require previous dilution are unsuitable for
capsules. If administered as such, they lead to irritation of the stomach.

GELATIN
It is the major component from which capsules are made. It has 5 basic
properties.
1. It is non toxic and can be used for food stuffs.
2. It is readily soluble in biological fluids at body temperature.
3. It is a good film forming material and produces a strong flexible film.
(The wall thickness of a hard gelatin capsule is about 100µm
4. Gelatin solution of high concentration- 40% w/v is mobile at 500c.Other
biological polymers e.g. Agar are not
5. A gelatin solution in water or in a water plasticizer blend undergoes a
reversible change from solution to gel at a few degrees above ambient.
For other dosage forms forming films, large quantities of heat is required to
cause change of state.

Gelatin is prepared by hydrolysis of collagen the main protein constituent of

connective tissue.
The raw materials include animal skins and bones.

Types of Gelatin
There are two main types:
1. Type A – Produced by acid hydrolysis
2. Type B – produced by basic hydrolysis
Acid hydrolysis takes 7-10 days. It is used on animal skins that require less pre-
treatment compared to bones.

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Basic hydrolysis takes 70-100 days and is used for bovine bones. The bones are first
decalcified by washing in acid to give a soft sponge like material called ossein.
Calcium phosphates are produced as byproducts. Ossein is then soaked in lime
pits for several weeks.
After hydrolysis, gelatin is extracted from the treated material using hot water.
The first extract contains gelatin with the highest physical properties. As the
temperature is raised, the quality of gelatin falls.
The weak solution of gelatin is concentrated in a series of evaporates then chilled
to form a gel. The gel is extruded to form stands which are dried in a fluidized
bed drier. The dried material is then graded and blended.

Bloom Strength and viscosity

Bloom strength is a measure of gel rigidity. It is determined by preparing a
standard gel ( 6.66 w/v) and maturing it at 100.
It is defined as the force in grams required topush a standard plunger 4mm into
the gel.
Gelatin used in hard capsule manufacture is of ahigher bloom strength (200 –
250gms) than that for soft capsules 150grams.
Student assignment
Read on colourants
Sizes of Capsules
Capsule shells are supplied in a number of sizes ranging from 000 to 5.
0 is the largest while 5 is the smallest.
The amount of medicament that can be filled in a particular size of capsule
depends on the density of the material to be filled.

For powders, the weight equals to body volume x tapped bulk density.
For liquids, the fill weight is equal to specific gravity x the capsule volume x 0.8

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Shapes of Capsules
Capsule shape has remained unchanged since its invention. Self locking
capsules were introduced in the 1960’s. This was to overcome spilling caused by
vibration that caused the capsule to come apart.
They have indents on the inside of the cap and the outside of the body.
When the capsule is closed after filling, they form a fit that holds them together
during mechanical handling.
Packaging and Storage of Capsules
Capsules should be packed in well closed glass or plastic containers and stored
in a cool place.
These containers are better than cardboard boxes as they are more convenient to
handle and transport.
They also protect the capsules from moisture and dust.

To prevent the capsules from rattling, a tuft of cotton is placed over and under
the capsules.
In containers with very hygroscopic capsules, a packet containing desiccant like
silica gel or anhydrous CaCl2 is placed to prevent absorption of excessive
moisture by the capsule.
Capsules are packaged in strip packs which provide sanitary handling of
medicines and eases counting and identification.

Filling of Hard Gelatin Capsules

Each ingredient is weighed and finely powdered. They are mixed by trituration
to form a uniform powder.
The mixed powder is placed on a paper and spread with a spatula so as to make
a small pile.
Remove the cap from the capsule and hold it in the left hand.
Press the body repeatedly into the powder until it is filled.
Insert the cap on the body and weigh the capsule

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Each capsule of the same size must be kept in the other pan as a tare to ensure
the exact quantity of drug is filled.

The type of material to be filled:

-Should not react with gelatin
-Should not contain a high level of free moisture
-Should have a volume of the drug which doesn’t exceed the size of the capsule
available.
Substances to be avoided include:
-Formaldehyde which causes cross linking reaction that make the capsule
insoluble
-Substances containing free water which may be absorbed by gelatin causing it to
soften and distort.

Types of Materials for Filling Hard Gelatin Capsules

1. Dry solids – Powders
Pellets
Granules
Tablets
2. Semi solids Thermosoftening mixtures
- Thixotropic
- Pastes
3. Liquids - Non-aqueous liquids (without water)

Student assignment:
Read on the hand operated gelatin capsule filling machine

Hand operated and electrically operated machines are used for filling the
capsules for quick dispensing.

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Hand operated hard gelatin capsule filling machines consists of the following;
1. A bed 200 or 300 holes
2. A capsule loading tray
3. A pin plate having 200 of 300 pins corresponding the number of holes
of the bed and capsule loading tray
4. A lever
5. A handle
6. A plate fitted with rubber top.
The machines are generally supplied with additional loading trays, beds and pin
plates with various sizes of the capsules.
The machines are very simple to operate and can be dismantled and resembled.
Even unskilled workers can fill the capsule contents without much difficulty.
Small quantities of capsules can be cleared by wiping each capsule with surgical
gauze or clean cloth.
On large scale they can be rolled lightly in the folds of a clean towel or cloth
forward and backward until cleaned.

FORMULATION
Formulations must meet basic requirements.
1. Be capable of being filled uniformly to give a stable product.
2. Must release active contents in a form available for absorption by the
patient.
3. They must comply with official standards.

Powder Formulation
The capsule fill is a mixture of active ingredients and the excipients.
The powder selected depends on
1. The properties of the active ingredients
2. The dose, solubility, particle size and shape
3. The size of the capsule to be used.

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Types of Excipients
i. Diluents – To give the plug forming properties. (a diluent is a type of
thinner, they decrease the viscosity of the fluid.
ii. Lubricants – to reduce powder to metal adhesion
iii. Glidants- To improve powder flow. (by reducing interparticulate
friction)
iv. Wetting agents – to improve water penetration
v. Disintegrants – to produce disruption of the powder mass
vi. Stabilizers – to improve product stability

There are three main factors in powder formulation

1. Good flow – using free flowing diluents and glidants
2. No adhesion – using a lubricant
3. Cohesion – using plug forming diluents

Good flow contributes to uniform filling of capsules.

The powder bed from which the dose is measured needs to be homogenous and
packed reproducibly to achieve uniform fill weight.
Low dose active ingredients flow well when mixed with free flowing diluent e.g.
lactose.
When space is limited, glidants e.g. silica or lubricants e.g. magnesium stearate
are added.
Glidants and lubricants coat the surfaces of other ingredients.
Student assignment
Read on formulation and release of active ingredients

DIFFICULTY IN FILLING CAPSULES

1. Deliquescent /Hygroscopic powders

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A gelatin capsule contains water which is extracted by a hygroscopic drug
rendering the capsule very brittle leading to cracking. This is overcome by
adding an absorbent like MgCO3 and or Mg0 (inside the capsule)
The capsule must be packed in a tightly closed glass capsule vial.

2. Eutetic mixtures – some substances when mixed tend to liquefy or form a

pasty mass due to the formation of a mixture with lower melting point than
ambient.
When filling these substances, each troublesome ingredient is mixed with an
absorbent separately then they are mixed together and filled in capsules.
The absorbent used are MgO and kaolin.
The substances can also be mixed together to form a eutectic mixture then an
absorbent like MgO or kaolin is added.

3. Addition of inert powders

Inert powders – (diluents) are added when the drug to be filled in a capsule is of
a very small quantity
The smallest capsule requires at least 65mg of the substance to fill it.

4. Filling of granular powders

Some powders lacking adhesiveness and most granular powders are difficult to
fill in capsules by punch method as they are not compressible and flow out of the
capsule as soon as they are lifted from the pile of the powder into which they are
punched.
To overcome this, non-adhesive powders should be moistened with alcohol and
the granular powders should be reduced to powder before filling into the
capsule.

5. Incompatible Ingredients.

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Some manufacturers separate incompatible ingredients by placing one ingredient
in a smaller capsule then placing this smaller capsule in a larger capsule
containing the other ingredient of the formulation.
Forming one of the constituents as a pro-drug

Special Types of Capsules

a) Enteric coated capsules
These capsules do not disintegrate in the stomach or acidic media but break up
in the intestines or alkaline medium.
Enteric coating is given to various categories of drugs i.e.
(i) Those that cause irritation of the gastric mucosa and lead to nausea and
vomiting.
ii) Those that interfere with digestion e.g. tannins, silver nitrate and other
salts of heavy metals.
iii) Those which are unstable in the gastric fluids.
iv) Those that are specially needed for the treatment of the intestines e.g.
santonin a vermicide or antihelmintic.
v) Those which are required to produce delayed action of the drug.
Substances used for enteric coating of capsules include cellulose acetate
phthalate or a mixture of waxes with fatty acids of their esters.
b. Sustained release capsules
They release the drug slowly and continuously for a prolonged duration of
action. This maintains the MEC of the drug in the blood at a constant level
throughout the treatment period.
The finely powdered drug is converted into pellets of suitable size (1- 2mm
diameter.)
The pellets are divided into a number of groups e.g. ten groups. The first group
is kept untreated to produce rapid therapeutic effect.

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The other groups are coated with selected materials one group after another to
produce thickness of varying degrees e.g. group 2 -2 coatings group 3 – 3
coatings etc.
The total thickness of these coatings should be 0.1mm.
All of the groups, both coated and uncoated are filled into the capsules. Materials
used for coating include;
-Cellulose esters
-Fats
-Keratin
-Mixtures of bees wax
-Cernouba wax with gylceryl monostearate
c. Rectal Capsules
Soft gelatin capsules may be used as substitutes for rectal of vaginal
suppositories
Different shapes and sizes are used.
They are generally wider at one end.
The movement of the sphincter muscles forces the capsule forward into the
rectum.
Liquids and solids can be filled in rectal capsules but the base in which the
medicament is incorporated must be non-toxic, non irritant and compatible with
the capsule shell.
d. Capsule for packing ophthalmic ointments
Ophthalmic ointments must be sterile and non irritant and remain so until the
whole product is used up.
The best method is to pack into single dose containers. Soft gelatin capsules are
used.
Just before application, the capsule is punctured with a sterile needle and the
contents instilled into the eye and the shell discarded.

Standardization of Capsules

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Capsules should be subjected to the following test
i. Shape and size
ii. Colour
iii. Thickness of capsule shell
iv. Locking test for semi solids and liquid ingredients for soft
capsules
v. Disintegration test
vi. Weight variation test
vii. Percentage of medicament test

The control tests in the official books are;

1. Disintegration test
A tablet disintegration apparatus is used. One capsule is placed in each tube
which is then suspended in beakers to move up and down for 30 minutes.
The capsules pass the test if no residue of drug or other fragments of the shell
remain on a screen mesh no. 10.
2. Weight variation test
20 capsules are taken at random and weighed. Their average weight is
calculated then each capsule weighed individually. The capsules pass the test if
the weight of individual capsules falls within 90-100% of average weight.
3. Contents uniformity tests
This is applicable to all capsules for oral administration.
A sample of the contents is assayed as described in the monographs. The values
calculated must comply with the prescribed standards.
Student assignment
Read on soft gelatin capsules

SOFT GELATIN CAPSULES

They are also referred to as soft gels.

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They consist of a liquid of semi-solid matrix inside a one piece of outer gelatin
shell.
They are soft and elastic in nature prepared from gelatin and water to which
glycerine, sorbitol or propylene glycol is added as a plasticizer making the
capsule flexible.
They contain a preservative to prevent the growth of bacteria of fungi. The
shapes include spherical, oval, cylindrical etc.
Contents vary from 0.1mm to 30mm.
Soft gelatin capsules are formed and filled in one continous operation of semi-
automatic machines.
They are hermatically sealed.
They are used for filling liquids and semi-solids e.g cod liver oil, Vitamin A,
Vitamin D and Multi vitamins.
Uses
1. They also contain eye, ear, nose, throat preparations
2. Opthalmic ointments are packed in unit dose capsules
3. They are also substitutes for suppositories

Preparation of soft capsules

These methods are used
1. Plate process
2. Rotary die process
1. Plate process
A warmed sheet of plasticized gelatin is placed over a plate having a no. of
depressions or moulds. The sheet is drawn into these depressions by applying a
vacuum
A measured quantity of liquid medicament is poured over then another shit of
gelatin is placed on.
Over these another plate of the mould is placed and pressure is then applied to
the combined plates.

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The capsules are then simultaneously shaped, filled and sealed into individual
units.
2. Rotary die process
The filled capsules are produced continuously and automatically. Two
continuous sheets of gelatin are supplied to the two die rolls of the machine that
has a number of matching dies and rotates at the same speed and in opposite
directions.
As the gelatin sheet comes in between the rollers, the material to be filled is
injected through a metering device.
The pressure exerted by the material forces the gelatin sheet to go into the
cavities of the die rolls to form two halves of the capsule and fill them.
The heat and pressure exerted by the die falls seals and cuts out the capsules.
The finished capsules are then passed through a series of napha baths to remove
lubricants and then dried.
The rotary machines can produce 2500 – 30,000 capsules per hour.

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