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

The potential use of phloretin, a polyphenolic compound, as a penetration e nhancer in the transdermal delivery of lignocaine hydrochloride (L-HCl) has been investigated. Standard in vitro skin permeation methods, using excise d human skin, were used to characterize the percutaneous absorption of L-HC l. Initially, phloretin was applied to the skin surface as a methanolic sol ution. The skin samples were treated 12 h prior to application of the ligno caine donor solution, which was buffered at pH 4.0 and 7.0. The data obtain ed 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 amo unt 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, pr essure area isotherms were recorded on a Langmuir-Blodgett trough using the model skin lipid ceramide-a. They showed a slight increase in the area occ upied per lipid molecule of 1.04 nm(2) at constant surface pressure. This r esult indicates an interaction between the model lipid and phloretin. The r esults suggest the potential use of phloretin as penetration enhancer in th e delivery of L-HCl through skin. (C) 2001 Wiley-Liss, Inc. and the America n Pharmaceutical Association J Pharm Sci 90:485-492,2001.