Pharmaceutical Manufacturing Handbook: Production and

HARD AND SOFT GELATIN CAPSULES 247
Capsules are usually more expensive dosage forms than an equivalent tablet
formulation due to the increased cost of the shells and the slower production rates.
Even with modern fi lling equipment, the fi lling speeds of capsule machines are much
slower than tablet presses. However, increased costs can be offset by avoiding a
granulation step. Capsules, although smoother and easy to swallow, also tend to be
larger than corresponding tablet formulations, potentially leading to retention in
the esophagus. Humidity needs to be considered during manufacture and storage,
with moisture leading to stickiness and desiccation causing brittleness. Cross - linking
of gelatin in the formulation can also lead to dissolution and bioavailability
concerns.
Capsule excipients are similar to those required for formulation of tablets and
include diluents, binders, disintegrants, surfactants, glidants, lubricants, and dyes or
colorants. The development of a capsule formulation follows the same principles as
tablet development, and consideration should be given to the same BCS issues. The
powder for encapsulation can comprise simple blends of excipients or granules
prepared by dry granulation or wet granulation. There is a reduced requirement for
compressibility, and often the fl ow properties are not as critical as in an equivalent
tablet formulation. The degree of compressibility required is the major difference,
and capsules can therefore be employed when the active ingredient does not possess
suitable compression characteristics.
4.1.6.2
Manufacture of Hard Gelatin Shells
Gelatin is a generic term for a mixture of purifi ed protein fractions obtained either
by partial acid hydrolysis (type A gelatin) or by partial alkaline hydrolysis (type B
gelatin) of animal collagen. Type A normally originates from porcine skin while B
is usually derived from animal bones, and they have different isoelectric points
(7.0 – 9.0 and 4.8 – 5.0, respectively) [6] . The protein fractions consist almost entirely
of amino acids joined together by amide linkages to form linear polymers, varying
in molecular weight from 15,000 to 250,000. Gelatin can comprise a mixture of both
types in order to optimize desired characteristics, with bone gelatin imparting fi rmness
while porcine skin gelatin provides plasticity. Gelatin Bloom strength is measured
in a Bloom gelometer, which determines the weight in grams required to
depress a standard plunger in a 6.67% w/w gel under standard conditions. Bloom
strength and viscosity are the major properties of interest for formulation of capsules,
and Bloom strength of 215 – 280 is used in capsule manufacture.
Gelatin is commonly used in foods and has global regulatory acceptability, is a
good fi lm former, is water soluble, and generally dissolves rapidly within the body
without imparting any lag effect on dissolution. Gelatin capsules are strong and
robust enough to withstand the mechanical stresses involved in the automated fi lling
and packaging procedures.
In addition to gelatin, the shells may contain colorants, opacifi ers, and preservatives
(often parabens esters). There are eight standard capsule sizes, and the largest
capsule size considered suitable for oral use is size 0 (Table 5 ).
To manufacture the shells, pairs of molds, for the body and the cap, are dipped
into an aqueous gelatin solution (25 – 30% w/w), which is maintained at about 50 ° C
in a jacketed heating pan. As the pins are withdrawn, they are rotated to distribute
the gelatin evenly and blasted with cool air to set the fi lm. Drying is carried out by