Evaluation of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) gels as a release vehicle for percutaneous fentanyl

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 2O )=2.24±0.47×10 −6 cm s −1 vs. ( P 46% block copolymer)=0.93±0.23×10 −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.