Thepurpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA)\npolymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics,\nRisperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content,\nbuffer pHand temperature on polymer molecular weight and degradation,were examined via a series of experiments and compared\nagainst a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight\nreduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation\nbetween the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres.\nSubsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo\nfirst order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was\ndependent on temperature, not pH. The findings of these studies show that encapsulation of weakly basic nucleophile type drugs\ninto PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere\ndrug delivery systems.
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