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Date of Award

1998

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Pharmaceutics and Medicinal Chemistry

First Advisor

Ravindra Vasavada

First Committee Member

Madhukar Chaubal

Second Committee Member

Patrick Jones

Abstract

In the present study, the effects of selected concentrations (0, 0.375, 0.75, 1.5 and 2.25% w/w) of ethyl oleate or oleic anhydride, the latentiated forms of catalyst oleic acid, were compared with regard to the release characteristics of metronidazole (1 0% w/w) from poly( ortho esters) films in distilled water at 3 7 °C. The rate of release of metronidazole from poly(miho esters) films was dependent on the ethyl oleate or oleic anhydride concentrations. The poly(ortho esters) films with adjuvants demonstrated slower drug release for all concentrations of ethyl oleate studied and for 0.375% and 0.75% w/w of oleic anhydride. The effects of drug loading (5, 7.5 and 10% w/w) and film thickness (150 to 400 !J.m) were also studied in the presence of 0.75 %w/w of either adjuvant. Increasing drug loading enhanced the rate of drug release from films of same thickness. However, variation of film thickness (150 to 400 !J.m) did not significantly alter the release profile possibly due to high concentration of the drug in the film (10% w/w). Gel permeation chromatography, scanning electron microscopy and near zero-order release, in vitro, suggested that the steady-state release of metronidazole from the poly( ortho esters) films following the burst effect occurred initially by a combination of diffusion and surface erosion of the polymer. Later, the release was further complicated by onset of bulk erosion of the polymer due to catalysis by oleic acid produced by ester or anhydride hydrolysis.

Pages

79

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