M. Alola et al., In vitro evaluation of biodegradable epsilon-caprolactone-co-D,L-lactide/silica xerogel composites containing toremifene citrate, INT J PHARM, 181(2), 1999, pp. 181-191
Poly(epsilon-caprolactone-co-D,L-lactide) polymers were blended with toremi
fene citrate or with toremifene citrate impregnated silica xerogel in order
to develop a controlled release formulation. The copolymers were synthesiz
ed by bulk polymerization and characterized by nuclear magnetic resonance,
size exclusion chromatography and differential scanning calorimetry analyse
s. 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 degrees C. The in vitro release studies in
dicate that the release flux of toremifene citrate increases with increasin
g weight fraction of caprolactone in the copolymer. Silica xerogel had a mi
nor 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 con
trolled manner because of the burst effect. The fraction of toremifene citr
ate released from PLA-CL80 matrix increased with the increasing loading of
toremifene citrate. The results of the study indicate that the in vitro rel
ease of toremifene citrate can be adjusted by varying the polymer compositi
on and also the initial drug loading. (C) 1999 Elsevier Science B.V. All ri
ghts reserved.