Effect of the molecular weight of poly(ε-caprolactone-co-DL-lactide) on toremifene citrate release from copolymer/silica xerogel composites

The purpose of this study was to develop a biodegradable polymeric carrier system for toremifene citrate based on epsilon -caprolactone/DL-lactide copolymers and silica xerogel. The effect of the molecular weight of poly(epsilon -caprolactone-co-DL-lactide) affecting the release rate of toremifene citrate from copolymer/silica xerogel composites was evaluated by in vitro dissolution study. Lower and higher molecular weight copolymers (LMW 60 000 g/mol and HMW 300 000 g/mol) were used in the devices. Drug release was compared from the (copolymer/drug) matrix device and the (copolymer/drug impregnated silica xerogel) composite device. Hydrolysis of the copolymer devices was evaluated by water absorption, weight loss and change of molecular weight by size exclusion measurements (SEC). Controlled release of toremifene citrate was obtained from both matrix and composite devices and the release rate was most affected by the initial molecular weight of the copolymer. Throughout the study better results were obtained with LMW devices, since drug release was steady for nearly 1 year and no changes in the release rate were observed. The drug release was diffusion controlled from both LMW matrix and composite devices. Incorporation of toremifene citrate into the silica xerogel was found to enhance the drug release rate. The copolymer matrices degraded by random hydrolytic chain scission and, unexpectedly, HMW P(CL/LA) degraded faster than LMW P(CL/LA). The release of toremifene citrate from HMW devices was not complete before the second stage of polymer degradation began. (C) 2001 Elsevier Science B.V. All rights reserved.