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Release of leuprorelin, an LHRH agonist, from injectable microcapsules and degradation of its biodegradable polymer [( d,l -lactic-glycolic) acid 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, salt concentration and osmolarity of dispersion medium changed drug release. Weight loss along with the decrease of the molecular weight of PLGA was delayed in the in vitro release test system that successfully predicted 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 glycolic acid in the polymer as another indicator of the degradation increased similarly as a function of the PLGA weight loss in both systems. Judging from the fact that resembling drug release was acquired despite the different degradation rate of matrix, distinctive mechanism governs the drug release in the in vitro release test system. |
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