An ether derivative of menthol, O-ethylmenthol had an excellent activity toward the in vivo percutaneous absorption of ketoprofen alcoholic hydrogels through the rabbit skin [30e33]. Based on this finding, a series of mono- and disubstituted derivatives of cyclohexane with an O-ethyl group were synthesized and evaluated for their absorption enhancement activity [34]. Most of them acted better than O-ethylmenthol, except for methyl-substituted products. However, the irritation potency of these derivatives correlated well with their enhancing activity. As an exception, 1-O-ethyl-3-butylcyclohexanol (OEBC) was proved to be a safe and potent enhancer for ten different model drugs [35]. In addition, thiomenthol derivatives were also synthesized
