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Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs


Affiliations
1 Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, United States
2 Evonik Inc., 750 Lakeshore Parkway, Birmingham, AL 35211, United States
3 Section of Pharmaceutical Chemistry, Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
4 University of Kentucky College of Pharmacy, Lexington, KY 40536, United States
 

The purpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA) polymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics, Risperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content, buffer pH and temperature on polymermolecularweight and degradation, were examined via a series of experiments and compared against a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight reduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation between the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres. Subsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo first order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was dependent on temperature, not pH.The findings of these studies show that encapsulation of weakly basic nucleophile type drugs into PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere drug delivery systems.
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  • Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

Abstract Views: 97  |  PDF Views: 6

Authors

Susan D'Souza
Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, United States
Jabar A. Faraj
Evonik Inc., 750 Lakeshore Parkway, Birmingham, AL 35211, United States
Rossella Dorati
Section of Pharmaceutical Chemistry, Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Patrick P. DeLuca
University of Kentucky College of Pharmacy, Lexington, KY 40536, United States

Abstract


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