Source: http://saffron.pharmabiz.com/article/detnews.asp?

articleid=40482&sectionid=46
Hard (two-piece) capsules were developed as an edible container of
medicine(s), mainly for oral use. These two-piece capsules have been
used for over a century for pharmaceutical purposes. J. C. Lehuby, a
Frenchman, is credited with the invention of the two-piece capsule. He
was granted a French patent in 1846 for a method of making 'medical
coverings'. However, J. Murdoch of London, in 1848, was the first to create
two-piece capsule, which was made from the sole use of animal-based
gelatin. The design of this original hard shell capsule has remained
unchanged over the decades except for changes in shape to create selflocking tamper-resistant capsules and in sealing process to allow pastes
and liquids to be filled into capsules. In addition to having the advantages
of elegance, ease of use, capsules (especially hard shells) enjoy widespread popularity, because of their relative ease of manufacturing and
their ability to efficiently mask the taste and odour of the medicines. As a
result of the advances made in drug delivery technology during the last 20
to 30 years, the importance of capsules as delivery device has increased
enormously.
Substitute for gelatin
Until recently capsules refer to 'gelatin' capsules i.e. the capsule shells are
made from gelatin. The default material for the two-piece hard capsules is
gelatin. The raw material gelatin is derived from animal source, primarily
collagen. The collagen, a fibrillary protein, forms the connective and
supportive tissues of mammalian (bovine and swine) body. Gelatin has
been the raw material of choice due to its ability to undergo a reversible
phase change from a solution to gel at a temperature only few degrees
above ambient, which enables a homogenous film of gelatin to be
prepared easily. Today, however, several materials have been investigated
as a substitute for the classic gelatin in the two-piece hard shell capsules.
Hydroxypropyl methylcellulose (HPMC), also known as hypromellose, has
become a successful alternative material for hard shell gelatin capsules
and is actually on the market. HPMC capsules are made of plant-derived
(cellulose derivatives) material and do not contain components of animal
origin. Another non-animal capsule material pullulan, a water-soluble
polysaccharide produced through a fermentation process, has achieved
regulatory acceptance.
Emergence of gelatin substitute
The success achieved by the hard gelatin capsules, popularly known as
HGC, is well known and is reflected by the fact that hard gelatin capsule
shells have been used in the pharmaceutical field for more than 100 years
and continue to grow in acceptance as the preferred oral dosage form.

Hard gelatin capsules do have some drawbacks. The principal drawback of

hard gelatin capsules is that capsule shells have 13 to 16 per cent water
content and therefore may not be suitable for use with readily
hydrolysable drugs. Some drugs react with amine groups of gelatin,
causing formation of cross-link between gelatin molecules and reducing
the solubility of the capsule shell. Furthermore, gelatin products are
avoided by many as a result of religious, cultural or vegetarian
restrictions. In addition, recent safety report suggests a theoretical risk of
transmitting spongiform encephalopathy via gelatin capsules.
To overcome these problems, pharmaceutical scientists have been
working for decades to develop capsules made of starch, cellulose
derivatives and polyvinyl alcohol copolymer. In 1998, Shionogi Qualicap
successfully manufactured HPMC capsules, Quali-V, with properties
suitable for pharmaceutical products and dietary supplements. Quali-V is
the first HPMC capsule developed for pharmaceutical market, can be filled
with many kinds of liquid or semisolid dosage forms. Today, HPMC
capsules are produced by many manufacturers; viz. Vcaps by Capsugel
division of Pfizer, Cellulose capsules by Natural Capsules Ltd., and
Naturecaps by Associated Capsules.
HPMC capsules
HPMC capsules can be manufactured by the same dipping and forming
method that is employed for the manufacture of classic hard gelatin
capsules. Various grades of HPMC are suitable for forming the two-piece
shells and are accepted by the pharmacopoeias of the US, Europe and
Japan. As HPMC alone gels at temperatures above 60 degree Celsius,
small amounts of carrageenan as a gelling agent and potassium chloride
as a co-gelling agent are added to the HPMC solution to enable gelling at
lower temperatures (45 to 55 degree Celsius). HPMC capsules available
are different from each manufacturer because each uses own patented
gelling system using different techniques and additives to solve specific
issues related to gel formation. Thus HPMC capsules, unlike gelatin
capsules, from different manufacturers are not interchangeable.
HPMC capsules are odourless, flexible and exhibit similar dissolution
character to the hard gelatin capsules. The main difference in their
physicochemical properties from gelatin capsules, as mentioned earlier, is
that their moisture content is less, 2 to 5 per cent as opposed to 13 to 16
per cent for gelatin, and water does not act as a plasticizer for the HPMC
shells and thus maintain mechanical integrity under low-moisture
conditions. Dissolution profiles of HPMC and gelatin capsules are
comparable over a wide range of pH values. Studies describing the
bioavailability of drugs, as reported till date, show that oral bioavailability
in HPMC capsules is identical to that delivered in gelatin capsules.
HPMC capsules have been widely used in the nutritional market. To date,

HPMC capsules have been successfully utilized for pharmaceutical

products on the Japanese market. There are a few pharmaceutical
products on the world market. Many giant companies are actively
including HPMC capsules in their developmental studies.
Conclusion
HPMC capsules offer numerous and unique benefits as dosage form for
pharmaceuticals. Among the long list of advantages, perhaps one of the
most significant is that non-animal sources capsule allows consumers for
addressing a variety of cultural and dietary requirements. These capsules
avoid concerns about the spread of animal originated disease. The
property of mechanical integrity even at low shell moisture content enable
its use in dry powder inhalers (DPIs) and in formulations containing waterunstable drugs. Increasing commercial availability, offer of overcoming
problems inherent with gelatin capsules coupled with their rapid progress
in manufacturing; make HPMC capsules an ideal alternative to classic
gelatin capsules.