Unstirred Water Layer Effects on Biodegradable Microspheres

Abstract

This study explores the mechanistic aspects of in vitro release from biodegradable microspheres with the objective of understanding the effect of the unstirred water layer on polymer degradation and drug release. In vitro drug release experiments on Leuprolide PLGA microspheres were performed under “static” and “continuous” agitation conditions using the “sample and separate” method. At specified time intervals, polymer degradation, mass loss, and drug release were assessed. While molecular weight and molecular number profiles for “static” and “continuous” samples were indistinct, mass loss occurred at a faster rate in “continuous” samples than under “static” conditions. In vitro results describe a fourfold difference in drug release rates between the “continuous” and “static” samples, ascribed to the acceleration of various processes governing release, including elimination of the boundary layer. The findings were confirmed by the fourfold increase in drug release rate when “static” samples were subjected to “continuous” agitation after 11 days. A schema was proposed to describe the complex in vitro release process from biodegradable polymer-drug dosage forms. These experiments highlight the manner in which the unstirred water layer influences drug release from biodegradable microspheres and stress the importance of selecting appropriate conditions for agitation during an in vitro release study.