In vitro evaluation of biodegradable ε-caprolactone-co-D,L-lactide/silica xerogel composites containing toremifene citrate

Poly(ε-caprolactone-co-D,L-lactide) polymers were blended with toremifene citrate or with toremifene citrate impregnated silica xerogel in order to develop a controlled release formulation. The copolymers were synthesized by bulk polymerization and characterized by nuclear magnetic resonance, size exclusion chromatography and differential scanning calorimetry analyses. The in vitro release of toremifene citrate, an antiestrogenic compound, and silica was carried out in simulated body fluid (pH 7.4) containing 0.5 wt% sodium dodecylsulphate at 34°C. The in vitro release studies indicate that the release flux of toremifene citrate increases with increasing weight fraction of caprolactone in the copolymer. Silica xerogel had a minor enhancing effect on the release rate of toremifene citrate. Copolymers containing larger amounts of D,L-lactide (PLA-CL20 and PLA-CL40 copolymers) were not suitable matrices for the delivery of toremifene citrate in a controlled manner because of the burst effect. The fraction of toremifene citrate released from PLA-CL80 matrix increased with the increasing loading of toremifene citrate. The results of the study indicate that the in vitro release of toremifene citrate can be adjusted by varying the polymer composition and also the initial drug loading. Copyright (C) 1999 Elsevier Science B.V.