Promoting effect of 2-n-alkylcyclohexanones on the percutaneous absorption of indomethacin.

Abstract

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.