PREPARATION AND CHARACTERIZATION OF POLYLACTIC ACID MICROSPHERES CONTAINING BOVINE INSULIN BY A W O/W EMULSION SOLVENT EVAPORATION METHOD/

The objective of this study was to produce polylactic acid (PLA) micro spheres containing bovine insulin as a sparingly water soluble model d rug using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, The preparative conditions were optimized, Employment of smal ler internal aqueous phase volume (50 mu l or 100 mu l) in the manufac turing process, resulted in the high loading efficiency (over 95% of t heoretical insulin loading efficiency), The addition of 10% (w/v) NaCl to the external aqueous phase (0.5% polyvinyl alcohol solution) reduc ed loading efficiency compared to the case where no NaCl was added to the external phase, The mean volume diameter for prepared PLA microsph eres was in the region of 15-25 mu m in all cases, PLA microspheres co ntaining 5% and 10% insulin theoretically exhibited burst release in t he initial stage, After a three week dissolution test, the surface of the microspheres became more porous due to the degradable characterist ics of PLA polymer itself, Nevertheless, about 80% of the insulin stil l remained undegraded in PLA microspheres. Finally, insulin-loaded PLA microspheres (corresponding to 4 I.U. insulin) were administered to n ormal rats subcutaneously, and the pharmacological effect (a decrease in serum glucose level) was demonstrated.