Sugar Ester J-1216 Enhances Percutaneous Permeation of Ionized Lidocaine

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. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4482-4490, 2011