title: Enantioselective penetration enhancing effect of carvone on the in vitro transdermal permeation of nicorandil.
abstract: The objective was to investigate the difference in penetration enhancing effect of R-carvone, S-carvone and RS-carvone on the in vitro transdermal drug permeation. In vitro permeation studies were carried out across neonatal rat epidermis from 2%w/v HPMC (hydroxypropyl methylcellulose) gel containing 4%w/v of nicorandil (a model drug) and a selected concentration (12%w/v) of either R-carvone, S-carvone or RS-carvone against a control. The stratum corneum (SC) of rats was treated with vehicle (70%v/v ethanol-water) or ethanolic solutions of 12%w/v R-carvone, S-carvone or RS-carvone. The enhancement ratio (ER) of R-carvone, S-carvone and RS-carvone when compared to control was about 37.1, 31.2 and 29.9, respectively indicating enantioselective penetration enhancing effect of carvone enantiomers. Furthermore, there was a significant decrease in the lag time required to produce a steady-state flux of nicorandil with S-carvone when compared to R-carvone and RS-carvone. DSC and FT-IR studies indicate that the investigated enantiomers of carvone exhibit a difference in their ability to affect the cellular organization of SC lipids and proteins thereby showing enantioselective transdermal drug permeation. It was concluded that R-carvone exhibited a higher penetration enhancing activity on transdermal permeation of nicorandil when compared to its S-isomer or racemic mixture.
authors.affiliation: College of Pharmacy, Nova Southeastern University, Pharmaceutical Sciences, Fort Lauderdale, Florida, USA. krishnaiah.yellela@fda.hhs.gov
authors.forename: Yellela S R
authors.initials: YS
authors.lastname: Krishnaiah
authors.forename: Aly
authors.initials: A
authors.lastname: Nada
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D008297:Male; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D020108:Nicorandil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000378:metabolism; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D014677:Pharmaceutical Vehicles; D014665:Vasodilator Agents; D020108:Nicorandil; C006923:carvone