In Vivo Release Profiles of Leuprolide Acetate from Microcapsules Prepared with Polylactic Acids or Copoly(Lactic/Glycolic) Acids and in Vivo Degradation of These Polymers

Abstract

To screen a suitable polymer for preparing a controlled-release dosage form effective for one month, square plates of polylactic acid (PLA) with average molecular weights of 6000 to 50000 and copoly(lactic/glycolic) acid (PLGA) with average molecular weights of 6000 to 13500 and a copolymer ratio of 90/10 to 55/45 were implanted in rats subcutaneously, and the weight losses were determined over l00d. Typically the pattern of weight loss was biphasic with a lag time followed by a period when the weight fell exponentially. The lag times and the half lives of the degradation period increased with increase in the molecular weight or with decrease in glycolide content. Release of leuprolide acetate from PLA microcapsules at the injection site in rats (in vivo release) tended to be comparable to the bioerosion rate of the polymer used as the wall substance, and the in vivo release of the drug from PLGA microcapsules tended to be comparable to the biodegradation rate of the polymer. The in vivo release profile of the drug from microcapsules prepared with PLGA of average molecular weight 14000 and copolymer ratio 75/25 was ideal for one month's controlled release. The in vivo release profile from microcapsules injected subcutaneously in rats was comparable to the in vitro release. © 1988, The Pharmaceutical Society of Japan. All rights reserved.