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1) Development and in vivo testing of a gastric retention device (GRD) in dogs : 2) product formulations and in vitro-in vivo evaluation of a) immediate release formulation of itraconazole, b) controlled-release formulation of ketoprofen in adults

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dc.contributor.advisor Ayres, James W.
dc.creator Kapsi, Shivakumar G.
dc.date.accessioned 2012-09-07T17:09:30Z
dc.date.available 2012-09-07T17:09:30Z
dc.date.copyright 1998-11-24
dc.date.issued 1998-11-24
dc.identifier.uri http://hdl.handle.net/1957/33331
dc.description Graduation date: 1999 en_US
dc.description.abstract 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. en_US
dc.language.iso en_US en_US
dc.subject.lcsh Drugs -- Controlled release en_US
dc.subject.lcsh Drug delivery systems en_US
dc.subject.lcsh Oral medication en_US
dc.title 1) Development and in vivo testing of a gastric retention device (GRD) in dogs : 2) product formulations and in vitro-in vivo evaluation of a) immediate release formulation of itraconazole, b) controlled-release formulation of ketoprofen in adults en_US
dc.type Thesis/Dissertation en_US
dc.degree.name Doctor of Philosophy (Ph. D.) in Pharmacy en_US
dc.degree.level Doctoral en_US
dc.degree.discipline Pharmacy en_US
dc.degree.grantor Oregon State University en_US
dc.contributor.committeemember Christensen, Mark
dc.contributor.committeemember Parrott, Keith
dc.contributor.committeemember Smith, Bradford
dc.description.digitization File scanned at 300 ppi (Monochrome) using Capture Perfect 3.0 on a Canon DR-9050C in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR. en_US
dc.description.peerreview no en_us


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