Transdermal iontophoretic delivery of arginine-vasopressin (I): Physicochemical considerations

Abstract

The enhancement in the transdermal delivery of arginine-vasopressin (AVP), a nonapeptide antidiuretic hormone (ADH), was studied using the Transdermal Periodic lontotherapeutic System (TPIS). The TPIS is capable of generating a pulse current at a specific combination of waveform, frequency and ON/OFF ratio. The in vitro permeation studies of AVP across the hairless rat skin was conducted under TPIS application and the results were compared with that by passive diffusion. Vasopressin was found to be relatively stable during the course of the experiment. The effect of pH and ionic strength of the donor solution and drug concentration on the AVP flux was evaluated. Under the application of TPIS, the transdermal delivery rate of AVP could be enhanced as much as 1000-fold and the degree of enhancement was noted to be dependent upon the physicochemical conditions used during the iontophoresis treatment. The flux of AVP at pH 5.0 and 7.4 was similar at constant ionic strength, but increased substantially as the ionic strength decreased. A linear relationship was established between AVP flux and AVP concentration in the donor compartment. The skin permeability enhanced by TPIS treatment is reversible and upon termination of iontophoretic application, the AVP flux was observed to return to that by passive diffusion alone.