Capsules1

PHR 221: Pharmaceutical Technology II

Course Teacher: Mohammad Nasir Uddin

Lecturer, Department of Pharmacy, NSU

Capsules

Capsules

Capsules are solid dosage forms in which medicinal agents are

enclosed within hard or soft soluble shell. The shells are

generally formed from gelatin.

The capsule is regarded as container drug delivery system that

provides a tasteless/ odorless dosage form without need for

secondary coating step.

Routes of administration

• Oral

• Rectal

• Vaginal

• As unit dose container for ophthalmic ointments

Advantages of capsules for oral administration

1. Conveniently carried

2. Readily identified

3. Swallowing is easy for most patients, aesthetically pleasing

4. Prescribing flexibility

5. Efficiently and productively manufactured

6. Packaged and shipped at lower cost and with less breakage

7. More stable and have a longer shelf-life

8. Empty hard gelatin capsules are often used in the extemporaneous

compounding of prescriptions

9. Taste and odor masking

Disadvantages of capsules

• The drugs which are hygroscopic absorb water from the

capsule shell making it brittle and hence are not suitable

for filling into capsules.

• The concentrated solutions which require previous

dilution are unsuitable for capsules because if

administered as such lead to irritation of stomach.

Characteristics of capsules

• Capsules are available in many different sizes and shapes and

can be used for the administration of powders, semisolids and

liquids.

• Unpleasant tastes and odors of drugs are effectively masked by

the practically tasteless capsule shell which dissolves or is

digested in the stomach after about ten to twenty minutes.

• Capsules also can be used as a means of providing accurately

measured doses for administration rectally or vaginally.

Capsule types

• Capsule may be classified depending on nature of shell

Hard gelatin capsule (Two piece)

Soft gelatin capsules (one piece)

Raw materials for capsule shell preparation

Gelatin: Main ingredient for making capsule shells.

FD & C and D & C colorant: To make capsules look distinctive and attractive.

Water: 12 to 16 % but may vary depending on the storage condition

Preservatives: To reduce the growth of microorganisms. sulfur dioxide which is

added as the sodium salts, bisulfite or metabisulfite, sorbic acid or the methyl

propyl esters of para hydroxy-benzoic acid and the organic acids, benzoic and

propanoic acids.

Wetting agents: To ensure that the lubricated metal moulds are uniformly

covered when dipped into the gelatin solution. E.g. of sodium lauryl sulfate.

Opaquants/ Opacifying agent: To make the shells opaque. e.g. titanium dioxide

Excipients in powder-filled capsule

Types of excipients used in Powder-filled capsule

Diluents,which give plug forming properties

Lubricants, which reduce powder to metal adhesion

Glidants, which improve powder flow

Disintegrants, which produce disruption of powder mass

Stablizer, which improve product stabilty

Gelatin

Gelatin possess some basic properties that make it suitable for the

manufacture of capsules:

1. It is non-toxic, widely used in foodstuffs and acceptable for use

worldwide.

2. It is readily soluble in biological fluids at body temperature.

3. It is good film-forming material, producing a strong flexible film

4. The gelatin films are homogeneous in structure, which gives them

strength.

5. Solutions of high concentration, 40% w/v, are mobile at 50°C. Other

biological polymers, such as agar, are not.

Production of gelatin

• Gelatin is produced by the hydrolysis of collagen. Animal skins

and bones (bovine or porcine) are the raw materials used for

gelatin manufacture.

• There are two main types of gelatin: type A , which is produced

by acid hydrolysis and type B, which is produced by basic

hydrolysis.

• The acid process takes about 7-10 days and is used mainly for

porcine skins while the basic process takes about 10 times as

long and is used for bovine bones.


• The bones must first be decalcified by washing in acid to give a

soft sponge like material called ossein, and calcium phosphates

are produced as a byproduct. The ossein is then soaked in lime

pits for several weeks.

• After hydrolysis, the gelatin is extracted from the treated

material using hot water.

• The resulting weak solution of gelatin is concentrated in a series

of evaporators and chilled to form gels.


• This gel is then extruded to form strand, which are then dried in

fluidized bed system. The dried material is graded and then blended to

meet the various specification required.

Hard gelatin capsules

The hard gelatin capsules:

• Used to manufacture most medicated agents, about 10 fold in

comparison to softgels

• Employed in clinical trials

• Used in the extemporaneous compounding

• The empty capsule shells consist of gelatin, sugar, water,

colorants (various dyes), and opaquants (titanium dioxide)


• Three major suppliers of empty gelatin capsules are:

Eli Lilly and Company

Capsugel

R. P. Scherer Corporation


Methods of preparation of empty hard gelatin capsule shells

The preparation methods of empty hard gelatin capsule shells

involves the following steps:

Dipping

Spinning or rotating

Drying

Stripping

Trimming

Joining



1. One hundred and fifty pairs of pins are dipped into a gelatin

solution to form caps and bodies simultaneously.

2. After dipping the pins are withdrawn from dipping solution and

are rotated to distribute the gelatin uniformly. During this time

the gelatin may be set or gelled by a blast of cool air.

3. The pins are moved through a series of controlled air drying

kilns or oven for the gradual and precisely controlled removal of

water.

Hard gelatin capsulesMethods of preparation of empty hard gelatin capsule shells

4. The capsules are stripped from the pins by bronze jaws and

trimmed to length by stationary knives.

5. After being trimmed to exact length, the cap and body sections

are joined and ejected from machine.



The entire cycle of the machine lasts approximately 45 min.

Thickness of the capsule wall is controlled by the viscosity of the

gelatin solution and the speed of time of dipping.

Other matters critical to the final dimensions are: mold pin

dimensions, precise drying, and machine control relating to cut

lengths. Precise control of drying conditions is essential to the

ultimate quality of the cast film.


Empty capsule properties

Empty capsules contain a significant amount of water that acts as

a plasticizer for the gelatin film and is essential for their function.

The standard moisture content specification for hard gelatin

capsules is between 13 % w/w and 16 % w/w.

This value can vary depending upon the conditions to which they

are exposed: at low humidity’s they will lose moisture and

become brittle, and at high humidity’s they will gain moisture

and soften.



The moisture content can be maintained within the correct

specification by storing them in sealed containers at an even

temperature.

Capsules are readily soluble in water at 37ºC.

When the temperature falls below this, their rate of solubility

decreases. At below about 30ºC they are insoluble and simply

absorb water, swell and distort.



This is an important factor to take into account during

disintegration and dissolution testing. Because of this most

pharmacopoeia have set a limit of 37ºC ± 1ºC for the media for

carrying out these tests. Capsules made from hypromellose have

different solubility profile, being soluble at temperatures as low

as 10ºC.


Capsule filling

Capsule sizes

Hard gelatin capsules are made in a range of fixed sizes. The standard

industrial sizes in use today for human medicines are from 0 to 4.

To estimate the fill weight for a powder, the simplest way is to multiply

the body volume by its tapped bulk density.

The fill weight for liquids is calculated by multiplying the specific

gravity of the liquid by the capsule body volume multiplied by 0.9.


Capsule filling

Capsule sizes

Capsule size Body volume (mL)

0 0.69

1 0.50

2 0.37

3 0.28

4 0.20


Capsule shell filling

Hard capsules can be filled with a large variety of materials of different

physicochemical properties.

The materials for filling into capsules should meet following criteria:

Must not react with gelatin

Must not contain a high level of free moisture

The volume of the unit dose must not exceed the sizes of

capsule available.


Capsule shell filling

The materials that have been filled into hard capsules can be

classified in three categories:

Dry solids: powders, pellets, granules, tablets

Semi solids: pastes, thixotropic mixtures, thermo softening

mixtures

Liquids: Non-aqueous liquids

Education

Capsules1