title: Sugar ester J-1216 enhances percutaneous permeation of ionized lidocaine.
abstract: Percutaneous absorption enhancers affect not only the permeability of skin but also the thermodynamic properties of active ingredients in the vehicle. The present study examined the effect of J-1216, a sucrose laurate with hydrophilic-lipophilic balance = 16, on the percutaneous permeation of lidocaine (LC) from this point of view. The percutaneous permeation of LC from aqueous vehicles (pH 6.0, 7.0, 8.0, and 10.0) with or without 1.5% J-1216 was examined with excised hairless mouse skin mounted on flow-through-type diffusion cell. The permeation of LC without J-1216 increased with an increase in the vehicle pH and could be basically explained by pH-partition theory. J-1216 increased the LC permeation at pH 6.0 and 7.0 but decreased it at pH 8.0 and 10.0. The interaction between LC and J-1216 was examined using an ultrafiltration technique. J-1216 micelles interacted predominantly with unionized LC. A theoretical calculation suggested that J-1216 enhances the permeability coefficient of ionized LC, whereas it has almost no effect on that of unionized free LC. J-1216 directly affects the skin to increase the permeation of ionized LC, whereas J-1216 micelles interact with unionized LC to decrease the permeation. The effect of J-1216 is therefore a function of vehicle pH and LC concentration.
authors.affiliation: Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya 468-8503, Japan. okamotoh@meijo-u.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakai
authors.forename: Chiemi
authors.initials: C
authors.lastname: Tokuyama
authors.forename: Kazumi
authors.initials: K
authors.lastname: Danjo
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008812:Mice, Hairless; D008823:Micelles; D008956:Models, Chemical; D015999:Multivariate Analysis; D010539:Permeability; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000779:Anesthetics, Local; D008823:Micelles; C018152:sucrose monolaurate; D013395:Sucrose; D008012:Lidocaine