The primary objective of this study was to investigate the feasibility of PEO-PPO-PEO copolymer gel as a release vehicle for percutaneous administration of fentanyl in vitro and in vivo. A cellulose membrane and nude mouse skin with series concentrations of PEO-PPO-PEO block copolymers were used to examine the sustained-release pattern and permeation of fentanyl. The in vivo percutaneous absorption was examined using rabbits to evaluate the preliminary pharmacokinetics of fentanyl with 46% PEO-PPO-PEO copolymer formulation patches. The micelle formation ability of this block copolymer and the penetration ability of PEO-PPO-PEO copolymer over time were also studied by pyrene fluorescence probe methods and the dynamic light scattering test. At a concentration of 46% at 37°C, PEO-PPO-PEO copolymers formed a gel and showed a pseudo-zero-order sustained-release profile. With increasing concentration of copolymer in the cellulose membrane transport, the apparent release flux of fentanyl (200 μg/ml) decreased to 1.09±0.19 μg cm-2 h-1. Assessment of the effect of the copolymer on nude mouse skin also showed a decrease in the apparent permeability coefficient [(P(H(2)O))=2.24±0.47x10-6 cm s-1 vs. (P(46% block copolymer))=0.93±0.23x10-7 cm s-1]. The preliminary pharmacokinetics of the fentanyl patch was shown to be in steady state within 24 h, and this was maintained for at least 72 h with an elimination half-life (t(1/2)) of 10.5±3.4 h. A fluorescence experiment showed polymeric micelle formation of PEO-PPO-PEO copolymers at 0.1% (w/w) within 50 nm micelle size and the PEO-PPO-PEO copolymers were able to penetrate nude mouse skin within 24 h. Thus, it appears that fentanyl preparations based on PEO-PPO-PEO copolymer gel might be practical for percutaneous delivery. Copyright (C) 2000 Elsevier Science B.V.
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