IN-VITRO RELEASE TEST SYSTEM OF (D,L-LACTIC-GLYCOLIC) ACID COPOLYMER MICROCAPSULES FOR SUSTAINED-RELEASE OF LHRH AGONIST (LEUPRORELIN)

Release of leuprorelin, an LHRH agonist, from injectable microcapsules and degradation of its biodegradable polymer [(D,L-lactic-glycolic) a cid copolymer: PLGA] matrix were investigated to optimize an in vitro release test system and to clarify the difference between the in vivo release and in vitro release test system. Many factors such as pH, sal t concentration and osmolarity of dispersion medium changed drug relea se. Weight loss along with the decrease of the molecular weight of PLG A was delayed in the in vitro release test system that successfully pr edicted in vivo drug release. Most remarkable difference in the change of the molecular weight of PLGA was shown by accumulation of degraded products of PLGA in in vivo, although the ratio of lactic acid to gly colic acid in the polymer as another indicator of the degradation incr eased similarly as a function of the PLGA weight loss in both systems. Judging from the fact that resembling drug release was acquired despi te the different degradation rate of matrix, distinctive mechanism gov erns the drug release in the in vitro release test system.