title: Evaluation of percutaneous absorption of midazolam by terpenes.
abstract: Midazolam is a highly lipophilic drug that is widely used in preanesthetic medication. Recently, terpenes have been reported to show an enhancing effect on percutaneous absorption of drugs. The effect of terpenes (l-menthol, d-limonene, RS-(+/-)-beta-citronellol, geraniol) on the in vitro percutaneous absorption of midazolam through rat skin was evaluated using unjacketed Franz diffusion cells. Since midazolam is a lipophilic drug, percutaneous penetration is low and a percutaneous penetration enhancer is necessary for its percutaneous absorption. The terpenes (5%, w/v) in combination with 30% ethanol, and 20% propylene glycol significantly increased the percutaneous absorption of midazolam in comparison to the control. In vitro data suggested that d-limonene is the most effective enhancer among terpenes and other penetration enhancers such as Azone. In in vivo percutaneous absorption assays, the midazolam formulation using d-limonene could penetrate through rat skin, but the other terpenes could not penetrate. In conclusion, d-limonene in combination with ethanol can be used to enhance the percutaneous absorption of the highly lipophilic drug midazolam.
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ota
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito