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ACTA Pharmaceutica Sciencia
2006 , Vol 48 , Num 3
DELIVERY OF METOPROLOL BY ESTERIFICATION: A COMPARISON OF PASSIVE PERMEATION AND IONTOPHORESIS
PES College of Pharmacy, 50 Feet Road, Hanumanth Nagar, Bangalore, Karnataka, India
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The present work is an attempt to assess the permeability potential of metoprolol by combining the prodrug approach and iontophoresis. Two ester prodrugs of metoprolol were synthesized (metoprolol acetate and propionate), characterized and studied for their physicochemical properties and stability. In vitro permeation studies were carried out by anodal iontophoresis (0.5 mA/ cm2) through porcine skin using a Franz diffusion cell at different donor concentrations (5, 10, and 20mM). Evaluation of the physicochemical parameters showed significant increase in lipophilicity and a slight reduction in pKa values for prodrugs. The esters were found to be more stable in acetate buffer (pH 4) than phosphate buffer (pH 6). Passive permeation of prodrugs and iontophoresis of pure drug showed higher permeation at all concentrations. In nut shell, both prodrugs approach and iontophoresis enhanced the flux values independently but the combination contributed minimally.
Keywords :
TRANSDERMAL, PRODRUGS, METOPROLOL, IN VITRO, STABILITY, PARTITION COEFFICIENT