This document discusses capsules as a pharmaceutical dosage form. It describes capsules as solid dosage forms where medicinal agents are enclosed within gelatin shells. The document outlines the advantages and disadvantages of capsules, as well as characteristics such as sizes, shapes, and ability to mask tastes. It also discusses the production of hard and soft gelatin capsules, including details on gelatin production, capsule filling methods, and properties of empty capsule shells.

1. PHR 221: Pharmaceutical Technology II
Course Teacher: Mohammad Nasir Uddin
Lecturer, Department of Pharmacy, NSU

2. Capsules

3. 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.

4. Routes of administration
• Oral
• Rectal
• Vaginal
• As unit dose container for ophthalmic ointments

5. 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

6. 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.

7. 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.

8. Capsule types
• Capsule may be classified depending on nature of shell
 Hard gelatin capsule (Two piece)
 Soft gelatin capsules (one piece)

9. 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

10. 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

11. 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.

12. 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.

13. Production of gelatin
• 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.

14. Production of gelatin
• 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.

15. 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)

16. Hard gelatin capsules
• Three major suppliers of empty gelatin capsules are:
 Eli Lilly and Company
 Capsugel
 R. P. Scherer Corporation

17. Hard gelatin capsules
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

18. Hard gelatin capsules
Methods of preparation of empty hard gelatin capsule shells
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.

19. Hard gelatin capsules
Methods 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.

20. Hard gelatin capsules
Methods of preparation of empty hard gelatin capsule shells
 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.

21. Hard gelatin capsules
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.

22. Hard gelatin capsules
Empty capsule properties
 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.

23. Hard gelatin capsules
Empty capsule properties
 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.

24. Hard gelatin capsules
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.

25. Hard gelatin capsules
Capsule filling
Capsule sizes
Capsule size Body volume (mL)
0 0.69
1 0.50
2 0.37
3 0.28
4 0.20

26. Hard gelatin capsules
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.

27. Hard gelatin capsules
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