Studies on microencapsulation of 5-fluorouracil with poly(ortho ester) polymers.

Microencapsulation of 5-fluorouracil was successfully accomplished with poly(ortho ester) polymers by the emulsification-solvent evaporation method. While actual drug loading increased with increasing drug load (5-15% 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 ester) microspheres and provided controlled release of 5-fluorouracil. The volume of the aqueous phase was more important than the concentration of polyvinyl alcohol in it. The entrapment efficiency improved from 13 to 33% 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, entrapment efficiency and produced larger microspheres. The release studies conducted in 0.01 M phosphate buffer at 37+/-1.0 degrees C demonstrated that the release of 5-FU from the microspheres prepared with sorbitan sequioleate was nearly independent of the initial drug load with a mean zero-order rate constant of 0.0063% per hour. The data suggested that drug release was largely a diffusional process with contributions from dissolution and polymer degradation.