Abstract

The purpose of this study was to synthesize and determine the in vitro transdermal penetration of cytarabine and its 5-alkyl esters and to establish a correlation, if any, with selected physicochemical properties. The n-alkyl esters were synthesized by acylation of cytarabine (1) at its pharmacophoric 5-OH. The transdermal flux values of (1) and its esters were determined in vitro using Franz diffusion cell methodology. Aqueous solubility and log D (pH 7.4) values were determined and assessed for correlation to transdermal flux. An inverse relation was observed between the water solubility (Sw) and log D values. Of all esters, (4) exhibited the highest flux value of 22.2 nmol.cm-2.h-1, which is significantly different to that of the parent drug cytarabine (3.70 nmol.cm-2.h-1). No trend was found between water solubility and flux values.

Keywords: Transdermal penetration, cytarabine, promoiety, esters, physicochemical properties, log D. aqueous solubility, skin