Transdermal drug delivery using electroporation. II. Factors influencing skin reversibility in electroporative delivery of terazosin hydrochloride inhairless rats

A previous study indicated that the parameters governing the performance of electroporative delivery to the skin, are voltage, pulse length, number of pulses and electrode area.(1) This article describes a study in which the reversibility of the electroporation technique is evaluated with in vitro m ethods. The skin's reversal from an enhanced permeation mode as a result of electroporation to the base level was used as an index to understand the m echanism of drug delivery and also as a preliminary indicator of safety. Ma ximum delivery of the model drug, terazosin hydrochloride, occurred during the pulsing. Electroporative delivery with a wire electrode (small-area ele ctrode, 0.56 cm(2)) using 20 pulses at U-skin,U-0 88 V, and pulse length 20 ms, did not cause any damage to the skin. Increasing the pulse length to 6 0 ms, while keeping the rest of the parameters fixed, caused a visible chan ge in the external appearance of the skin. However, with the use of a spira l electrode (large-area electrode, 2.74 cm(2)) at 60-ms pulse length, there was minimal damage to the skin. This may be attributed to the more uniform flow of current over the whole skin area. The large-area electrode require d a smaller electrode voltage, U-electrode,U-O for any given U-skin,U-O and also delivered nearly double the instantaneous power density compared with the small-area electrode. These findings indicate that using shorter pulse s and large-area electrodes is a safer technique than large pulses and smal l-area electrodes when electroporation is used to enhance skin's permeabili ty for drug delivery. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceut ical Association J Pharm Sci 89: 536-544, 2000.