Transdermal penetration of zalcitabine, lamivudine and synthesised N-acyl lamivudine esters

The objective of this study was to determine the in vitro transdermal permeation through human epidermis of zalcitabine, lamivudine and the synthesised N-acyl lamivudine esters, with and without the use of Pheroid(TM) as delivery system and to establish a correlation, if any, with selected physicochemical properties. Six N-acyl lamivudine esters were prepared by acylation of lamivudine with six different acid chlorides. The experimental aqueous solubility, log D and in vitro transdermal flux values were determined for these compounds. There was an inverse correlation between the aqueous solubility and the log D values. The median flux of zalcitabine (0.442 mu mol/cm(2) h) in PBS was lower than that of lamivudine (4.289 mu mol/cm(2) h), but in Pheroid(TM), lamivudine (0.011 mu mol/cm(2) h) had a slightly lower median flux than zalcitabine (0.015 mu mol/cm(2) h). Entrapment of compounds in Pheroid was confirmed by confocal laser scanning microscopy. (C) 2007 Elsevier B.V. All rights reserved.