Study of the mechanisms of flux enhancement through hairless mouse skin by pulsed DC iontophoresis.

Enhanced iontophoretic transport using pulsed DC is usually explained by citing the observed decrease in skin resistance caused by an increase in AC pulse frequency at very small currents. Alternately, it has been suggested that the "on-to-off" nature of pulsed DC imparts an "impact energy" to the fluid, thereby increasing transport. This report provides a test of these mechanisms for enhanced delivery via pulsed iontophoresis. The DC resistance of hairless mouse skin during continuous and pulsed DC iontophoresis is measured as a function of time for selected pulse frequencies and duty cycles using current densities ranging from 0.1 to 1.0 mA/cm2. As a test of the impact energy mechanism, the iontophoretic transport of 14C-glucose measured with pulsed DC is compared with similar data obtained previously using continuous DC. It is suggested that pulsed current can yield lower resistance and enhanced drug delivery provided that (a) the "steady-state" current during the "on" phase of the pulse is very small and (b) the frequency is low enough to allow depolarization of the skin during the "off" phase of the pulse. The glucose transport results suggest that the "impact energy" concept does not apply to iontophoresis.