Enhancement of transdermal absorption by switching iontophoresis.

The enhancing effect of switching iontophoresis on transdermal absorption of phthalic acid (PA), benzoic acid (BA), salicylic acid (SA), p-phenylenediamine (PD), aniline (AN) and verapamil (VR) and its mechanism were examined. An electric current with pulsed waveform (4 kHz, 50% duty) was passed through the skin for 2 h at 10 V. Iontophoretic application was carried out with switching at intervals of 5, 10 and 20 min, or without switching. Each drug solution was injected into the donor side of the cell, and phosphate buffer (pH 7.4) was injected into the receiver side. Transport of PA, BA and VR was affected by switching the polarity of electrodes but no effect was observed on that of SA, PD and AN. Cumulative amount permeated and apparent permeability coefficients were apparently high at switching intervals with a short period. The partition coefficient suggested that there was no interrelation between the affinity for skin and the permeability of each drug. The resistance values of PA and glucose were low at intervals of 5 min suggesting the participation of enhanced hydration of the skin. These results suggested that enhancement of skin hydration plays an important role in the enhancing effect of switching iontophoresis on skin permeation.