Effect of cyclohexanone derivatives on in vitro percutaneous absorption of indomethacin.
We have previously shown that cyclohexanone derivatives exert a promoting effect on the in vivo percutaneous absorption of indomethacin (IMC), and now describe in vitro permeation studies to gain understanding of the mechanism of action. The results of the in vitro experiment were consistent with those of the previous in vivo experiments. 2-tert-Butylcyclohexanone was the most effective of six enhancers examined. The partition coefficient of IMC was determined in a buffer-octanol system containing the cyclohexanone derivatives, and the lipophilicities of these derivatives are discussed using a lipophilic index. We conclude that the cyclohexanone derivatives penetrate into the stratum corneum and alter the skin permeability of IMC by fluidizing or modifying the hard hydrophobic barrier of the corneum.
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
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Danyi
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Takayama
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Nagai
D000818:Animals; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D003510:Cyclohexanes; D003512:Cyclohexanones; D007213:Indomethacin