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 degrees 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 microgram/ml) decreased to 1. 09+/-0.19 microgram 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.
Department of Pharmaceutics, School of Pharmacy, Taipei Medical College, 250 Wu Hsing St., 110, Taipei, Taiwan. jhorng@tmc.edu.tw
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D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics; D005283:Fentanyl / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005782:Gels; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D011409:Propylene Glycols / Q000008:administration & dosage*; D011817:Rabbits; D012869:Skin Absorption
D000701:Analgesics, Opioid; D005782:Gels; D008823:Micelles; D014677:Pharmaceutical Vehicles; D011108:Polymers; D011409:Propylene Glycols; C012504:polypropylene glycol; D008353:Mannitol; D011092:Polyethylene Glycols; D004958:Estradiol; D005283:Fentanyl