#2 AGCAOILI,John Alsandair W.

2DPH
# HAGHANI RAD, Nilufar


Cole, Ewart T. 2000. Liquid-Filled and Sealed Hard Gelatin Capsule Technologies. Capsugel, 177-
189.
The main topic of this article is regarding liquid filled gelatin capsules, which has been develop
to accurately dose and seal liquids into hard gelatin capsules with the process of the technology. The
important concept focused by the author was more regarding the area of application of liquid filled and
hard sealed gelatin capsule, the outline of requirement formulation, its comparison with soft gelatin
capsule technology and the process for sealing hard gelatin capsules.
The author used many kinds of methods to collect his data. He used experimentation to test the
materials to be suitable filled. In connection in his experimentation, he observed the results by studying
the result that was given during the experiment. He used some existing sources that gave him
comparison with hard gelatin capsule and soft gelatin capsules. The author clearly stated his data
through many ways. He used a table showing that some excipients are not suitable for hard gelatin
capsules. He showed those materials that are compatible with hard gelatin capsules and some that are
not compatible. He gave comparison in some of the aspects that hard gelatin capsule differs from soft
gelatin capsules.
We can summarize the article content into following categories: One, almost all the categories
of drug examples of marketed products are already using the technology liquid filled hard gelatin
capsule. Two, regarding the comparison between hard gelatin capsule and soft gelatin capsules they are
identical which comprises gelatin, water, coloring and opacifying agents with the only different of
plasticizer and glycol which is only present in soft gelatin capsule. However in both it is important that
the filled material does not penetrate into the zone between the body and the cap before sealing
operation. Three, regarding the suitability of fill materials, since the tendency for poorly water soluble
drugs increases excipient supplies are developing new materials like SMEDDS (self-emulsifying drug
delivery system). Four, regarding the moisture exchange fill shell; typically a hard gelatin capsule
contains 13.5-1.5% moisture, which acts as a plasticizer for gelatin. A hygroscopic material, when filled
into the capsule, could extract moisture from the shell thereby inducing embrittlement. Five, regarding
the mechanical properties follows that monitoring of the mechanical properties of capsules stored at
various relative humidity is of critical importance determining compatibility between the fill materials
and the capsule shell. Six, regarding the dissolution stability indicator, certain excipients used in the
formulation of liquid filled capsules may have or may generate during storage, low levels of aldehydes
which can potentially react with gelatin. The rate of cooling can also have an influence on the structure
of certain excipients, which in turn may modify the drug release characteristics from the matrix itself.
Seven, regarding the recommended properties (temperature and viscosity) of fill materials are
important during liquid fill operation and in case of suspension the important thing is the size of
suspended drug.in practice of manufacturing if the viscosity is too low splashing of the bushing may
occur that may lead to contamination of the area overlap between the capsule body and cap and will
prevent a good seal to form. Absence of a clean break during dosing can lead to the same effect. Eight,
regarding the excipients compatibility with hard gelatin capsules they have been classified into three
arbitrary groups: lipophilic liquid vehicles, semisolid lipophilic vehicles/viscosity modifiers for lipophilic
liquid vehicles and solubilizing agents, surfactants, emulsifying agents and adsorption enhancers. Nine,
regarding filling and sealing equipment and essential part of a liquid-filling operation is the ability to
effectively seal the capsule. The supporting arguments are soft gelatin capsule process by Jimerson;
introduction of SMEDDS by Gattefosse and Sandoz; measuring the weight changes and various
conditions of relative humidity by Cade and Madit; changes in capsule brittleness with relative humidity
by Konty and Mulski; interaction of excipients or active ingredient with the shell changes the dissolution
behavior; technique of monitoring the interaction of excipients with the shell by Cade and Madit;
machines required for liquid-filled capsules by Cole; methods available to seal hard gelatin capsules by
Wittwer ; banding of hard gelatin capsules by Bowtle. The ideas are clearly presented through various
tables and complete explanation.
The author made a short conclusion about sealed hard gelatin capsule in observing his results
and collected data. He concluded that for modified formulations drugs, hard gelatin capsules provide
formulation scientist with possibility during the early stages of development in fast preparing products
in clinical trials. He also stated that process can be scaled-up to production level.
Yes, the data does support the conclusion. The data provided a clear difference in advantages of
the hard gelatinous capsules over the soft gelatinous capsules in both manufacturing and formulation.
Yes, the results are thought provoking but its better when there is enough evidence to prove the
provoked thoughts. In order to improve the research, there should have been more graphs in
comparison between hard gelatinous capsule and the soft gelatinous to support the tables provided. It
taught us that in formulating a dosage form everything should be considered not only the ingredients
but also the different dosage forms suitable for the medication.