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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 C. Vasavada

First Committee Member

Xiaoling Li

Second Committee Member

Silvio Rodriguez

Abstract

Microencapsulation of 5-fluorouracil was successfully accomplished with poly(ortho esters) polymer by emulsification-solvent evaporation method. While actual drug loading increased with increasing drug load (5 to 15% w/w), the entrapment efficiency remained essentially unaffected under a given set of experimental conditions. Incorporation of sorbitan sesquioleate enhanced entrapment efficiency, decreased the volume-surface mean diameter of the poly(ortho esters) microspheres and provided controlled release of 5-fluorouracil. The volume of aqueous phase was more important than the concentration of polyvinyl alcohol in it. The entrapment efficiency improved from 13 to 33% (w/w) when the volume of the aqueous phase was increased from 20 to 80 ml. The volume of organic phase (methylene chloride) and the concentration of polymer in it played an important role. The use of smaller volumes of more concentrated polymer solution enhanced actual drug loading and entrapment efficiency, and produced larger microspheres. The release of 5-FU from the microspheres prepared with sorbitan sequioleate was found to be nearly independent of the initial drug load with a mean zero-order rate constant of 0.0063 % per hr. The data suggested that drug release was largely a diffusional process with contributions from dissolution and polymer degradation.

Pages

86

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