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Transdermal penetration of cytarabine and its 5'-O alkyl ester derivatives
Lesetja J Legoabe1, Jaco C Breytenbach, David D N'Da
1Unit for Drug Research and Development, North West University, Private Bag X 6001, Potchefstroom, 2520, South Africa. lesetja.legoabe@nwu.ac.za
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 x cm(-2) x h(-1), which is significantly different to that of the parent drug cytarabine (3.70 nmol x cm(-)2 x h(-1)). No trend was found between water solubility and flux values.
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