Effect of drug lipophilicity and polar surface area on iontophoretic transdermal absorption.

Iontophoretic transdermal absorption of a series of β-biockers (atenolol, pindolol, metoprolol, acebutolol, oxprenolol, propranolol) was investigated by measuring the drug concentration in the skin. The objective of this study was to determine the effects of drug properties on the enhancement of drug concentration in the skin by iontophoretic delivery. Anodal iontophoresis of β-blocker was carried out by applying a constant direct current (0.5 mA/0.8 cm2, 30 min) to the drug solution (1 mg/mL), placed on the abdominal skin of anesthetized rat, and the drug concentration in the skin was measured by HPLC analysis. The enhancement effect of iontophoresis, represented as a ratio of drug concentration in the skin after iontophoresis to that after passive diffusion (without current), was exponentially attenuated with an increase in drug lipophilicity (the logarithm of 1-octanol/water partition coefficient at pH 7.4). On the other hand, when plotted against polar surface area (PSA) of drug molecule, the iontophoretic enhancement was linearly increased with increasing the PSA. The latter result implied that the transdermal absorption of drug having a strong interaction with water molecule was raised by iontophoresis. As a result, this study demonstrated that the PSA might be a useful parameter for clarifying the mechanism of iontophoretic enhancement and for optimizing the molecular structure of drug candidate to the iontophoretic delivery.