This thesis describes 1) development of a gastric retention device (GRD) to
increase gastric retention time of certain drugs, 2) product formulations of an immediate
release itraconazole and controlled-release ketoprofen. GRD was fabricated from crosslinked
carbohydrate polymers. Rate and extent of hydration of the film in water and in
simulated gastric fluid, compressibility of film, shape of the film, and in vivo gastric
transit time in the stomach of dog were used as tools to evaluate gastric retention
properties. Hydration studies were carried out at 37��C. Evaluation of the device
containing radio-opaque agents, in dogs for gastric retention was carried out with the help
of X-rays. The device was found to stay in the stomach of dogs for at least 10 hours.
GRD containing amoxicillin trihydrate caplets were evaluated in a human. The area
under the excretion rate curve was found to increase by 30% when compared to without
the device.
A successful development of a formulation of water insoluble itraconazole,
without the use of organic solvents, was achieved with modifications from eutectic
mixture techniques. Solubilization of the drug was achieved in polyethylene glycol of
higher molecular weight. A series of formulations made by varying the amounts
ingredients therein, were evaluated for dissolution profile in comparison with the
reference, Sporanox��. Effect of molecular weights of PEG and types of PEG were
evaluated for desired drug dissolution. Preliminary study from 6 subjects under the
conditions of fasting and fed indicated that bioavailability from the new formulation was
increased slightly when compared to the reference. This may be correlated to difference
in the rate of in vitro dissolution, where the new formulation has initial faster dissolution.
A controlled-release formulation of ketoprofen was also developed using a
diffusion-controlled polymer, which was coated onto the drug beads. Release of drugs
from such beads is controlled by the thickness of the coat. Thickness of the coat was
evaluated by SEM and was correlated to the desired in vitro drug release in comparison
to the reference Oruvail��. A three-way cross over study involving the new formulation
and two marketed products in 12 subjects under fasting conditions indicated that there
was a significant difference between the new product and marketed products, so as to be
considered non-bioequivalent. Use of In Vitro-In Vivo Correlations and Convolution-
Deconvolution relations predicted desired in vitro drug dissolution in a subsequent
modification of the formulation. / Graduation date: 1999
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/33331 |
| Date | 24 November 1998 |
| Creators | Kapsi, Shivakumar G. |
| Contributors | Ayres, James W. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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