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 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 micromol/cm2 h) in PBS was lower than that of lamivudine (4.289 micromol/cm2 h), but in Pheroid, lamivudine (0.011 micromol/cm2 h) had a slightly lower median flux than zalcitabine (0.015 micromol/cm2 h). Entrapment of compounds in Pheroid was confirmed by confocal laser scanning microscopy.
Gerber
Minja
M
Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa.
Breytenbach
Jaco C
JC
du Plessis
Jeanetta
J
D000279:Administration, Cutaneous; D004655:Emulsions; D004952:Esters / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019259:Lamivudine / Q000737:chemistry / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D012867:Skin; D012869:Skin Absorption; D012995:Solubility; D016047:Zalcitabine / Q000493:pharmacokinetics*
D004655:Emulsions; D004952:Esters; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine