J. Rich et al., Effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide)on toremifene citrate release from copolymer/silica xerogel composites, INT J PHARM, 212(1), 2001, pp. 121-130
The purpose of this study was to develop a biodegradable polymeric carrier
system for toremifene citrate based on epsilon -caprolactone/DL-lactide cop
olymers and silica xerogel. The effect of the molecular weight of poly(epsi
lon -caprolactone-co-DL-lactide) affecting the release rate of toremifene c
itrate from copolymer/silica xerogel composites was evaluated by in vitro d
issolution 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 com
pared from the (copolymer/drug) matrix device and the (copolymer/drug impre
gnated silica xerogel) composite device. Hydrolysis of the copolymer device
s was evaluated by water absorption, weight loss and change of molecular we
ight by size exclusion measurements (SEC). Controlled release of toremifene
citrate was obtained from both matrix and composite devices and the releas
e rate was most affected by the initial molecular weight of the copolymer.
Throughout the study better results were obtained with LMW devices, since d
rug 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 mat
rix and composite devices. Incorporation of toremifene citrate into the sil
ica xerogel was found to enhance the drug release rate. The copolymer matri
ces degraded by random hydrolytic chain scission and, unexpectedly, HMW P(C
L/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 degrad
ation began. (C) 2001 Elsevier Science B.V. All rights reserved.