Enhanced Percutaneous Absorption of Formoterol Fumarate via Pulsed Iontophoresis. II. Effect of Polarity, Pulse Frequency and Duty

To clarify the effect of polarity, pulse frequency and duty on the iontophoretic transport of formoterol fumarate (FF), in vitro and in vivo studies were performed with guinea pigs. In the in vitro studies, the flux at steady state was enhanced by the factor 7.61 with anodal iontophoresis in comparison with control, whereas, with cathodal iontophoresis it was restrained by the factor 0.79. When pulse frequency was varied from 0 to 40 kHz, the flux at steady state was enhanced with an increase in pulse frequency. In the in vivo studies with varying the duty of pulse potential from 10 to 100%, the maximum plasma concentration of FF was obtained at a 30% duty. In contrast, the plasma concentration of FF achieved at 100% duty was not high. With stripped skin, no significant difference in the plasma concentration of FF was shown between iontophoresis and control. Consequently, it is suggested that iontophoresis contributes to FF penetration across stratum corneum.