Promoting effect of 2-n-alkylcyclohexanones on the percutaneous absorption of indomethacin.
We previously evaluated the promoting effects of 2-tert-butylcyclohexanone and its analogues on the percutaneous absorption of indomethacin (IMC), and showed that the 2-position of the cyclohexanone ring plays an important role in drug permeability through the skin. The present study investigates the in vitro penetration enhancement of IMC by five 2-n-alkylcyclohexanone derivatives. 2-n-Octylcyclohexanone was the most effective enhancer, but the other four enhancers also had significant promoting actions on skin permeability of IMC. Maximum absorption enhancement was associated with a defined range of enhancer lipophilicity. We propose that the enhancer penetrates into the stratum corneum and improves skin permeability of a drug by dissolving some of the hard lipid components or modifying the dense lipid stratum corneum.
Quan
D
D
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Higuchi
R I
RI
Takayama
K
K
Higashiyama
K
K
Nagai
T
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000493:pharmacokinetics*; D008297:Male; D012869:Skin Absorption / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D003512:Cyclohexanones; D007213:Indomethacin