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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

The investigation focussed on the effects of oleic acid esters on the microencapsulation characteristics of the poly( ortho esters) polymer and their role as potential latentiated acid catalysts for the hydrolysis of the polymer backbone thereby influencing release of 5-fluorouracil. Four oleic acid esters, viz., ethyl oleate, propyl oleate, butyl oleate and lauryl oleate were studied. The microspheres were prepared by the emulsion solvent evaporation technique using sorbitan sesquioleate (6.44%w/w) as the surfactant. The microspheres were prepared with a theoretical drug loading of between 13 and 14% by weight and ester loading of 2.46% by weight with respect to the non-volatile components of the system. All the oleic acid esters (2.46% by weight) were found to retard the release of 5-fluorouracil from the microspheres. The maximum control over drug release was offered by ethyl oleate. Ethyl oleate was also found to give the highest percent entrapment of the drug in the microspheres. The release of 5-FU from the microspheres was inversely related to the concentration of ethyl oleate over the concentration range of 0.72% to 2.46% by weight. Gel permeation chromatography, scanning electron microscopy and the in vitro release data suggested that release of 5-FU from the microspheres occurred by a combination of diffusion and polymer erosion. The polymer erosion was further complicated by the by products of ester hydrolysis. Steady state drug release after the lag phase was zero-order. This suggested that polymer degradation in the steady state region erosion process initiated by oleic acid produced as a result of hydrolysis of the oleic acid ester during the release process.

Pages

103

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