Effect of phloretin on the percutaneous absorption of lignocaine across human skin.

The potential use of phloretin, a polyphenolic compound, as a penetration enhancer in the transdermal delivery of lignocaine hydrochloride (L-HCl) has been investigated. Standard in vitro skin permeation methods, using excised human skin, were used to characterize the percutaneous absorption of L-HCl. Initially, phloretin was applied to the skin surface as a methanolic solution. The skin samples were treated 12 h prior to application of the lignocaine donor solution, which was buffered at pH 4.0 and 7.0. The data obtained from the methanolic solutions at pH 4.0 show a 3.2-fold increase of the cumulative amount permeated after 24 h compared with the control. A second series of experiments were conducted using unilamellar phosphatidylcholine liposomes instead of methanol as a vehicle for the phloretin. The L-HCl amount permeated from liposomal-pretreated skin was 5.4-fold (p < 0.05) higher than the control within 24 h. In addition to the diffusion experiments, pressure area isotherms were recorded on a Langmuir-Blodgett trough using the model skin lipid ceramide-2. They showed a slight increase in the area occupied per lipid molecule of 1.04 nm(2) at constant surface pressure. This result indicates an interaction between the model lipid and phloretin. The results suggest the potential use of phloretin as penetration enhancer in the delivery of L-HCl through skin. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:485-492, 2001