Preparation and characterization of polylactic acid microspheres containing bovine insulin by a w/o/w emulsion...

The objective of this study was to produce polylactic acid (PLA) microspheres containing bovine insulin as a sparingly water soluble model drug using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The preparative conditions were optimized. Employment of smaller internal aqueous phase volume (50 microliters or 100 microliters) in the manufacturing process, resulted in the high loading efficiency (over 95% of theoretical insulin loading efficiency). The addition of 10% (w/v) NaCl to the external aqueous phase (0.5% polyvinyl alcohol solution) reduced loading efficiency compared to the case where no NaCl was added to the external phase. The mean volume diameter for prepared PLA microspheres was in the region of 15-25 microns in all cases. PLA microspheres containing 5% and 10% insulin theoretically exhibited burst release in the initial stage. After a three week dissolution test, the surface of the microspheres became more porous due to the degradable characteristics of PLA polymer itself. Nevertheless, about 80% of the insulin still remained undegraded in PLA microspheres. Finally, insulin-loaded PLA microspheres (corresponding to 4 I.U. insulin) were administered to normal rats subcutaneously, and the pharmacological effect (a decrease in serum glucose level) was demonstrated.