Controlled-release of leuprolide acetate from polylactic acid or copoly(lactic/glycolic) acid microcapsules: Influence of molecular weight and copolymer ratio of polymer.

Abstract

Polylactic acid (PLA) or copoly(lactic/glycolic) acid (PLGA) microcapsules containing leuprolide acetate were prepared by an in-water drying process and the release patterns were examined in vitro. The release rates were extremely small from microcapsules prepared with PLA of average molecular weight 22500, and from microcapsules prepared with PLGA having average molecular weight 21200 and a copolymer ratio of 75/25 (molar ratio of lactic acid to glycolic acid). The release rate of leuprolide acetate from the microcapsules prepared with PLA of average molecular weight 6000 was relatively fast, but was still too slow to give the desired drug level over one month. Several water-soluble compounds were incorporated into microcapsules prepared with PLA of average molecular weight 22500, in an attempt to increase the release rate by the creation of aqueous channels. These compounds only induced a high initial release and failed to increase drug release. The release profile of the drug from microcapsules prepared with PLGA of average molecular weight 14000 and a copolymer ratio of 75/25 was ideal for one month''s release. A small initial release was observed followed by a steady release which lasted for 35 d, and approximately followed zero-order kinetics.