INTERACTION BETWEEN PENETRATION ENHANCERS AND IONTOPHORESIS - EFFECT ON HUMAN SKIN IMPEDANCE IN-VIVO

Purpose: The objective of this study was to develop a non-invasive tec hnique to assess the interaction between chemical and electrical modes of percutaneous penetration enhancement in vivo. Methods: Impedance s pectroscopy, a non-invasive biophysical technique, was used to monitor the effect of iontophoresis on skin and to determine the extent to wh ich this effect was modulated by pretreatment with penetration enhance rs of different physicochemical properties. Results: Azone(R)/propylen e glycol and sodium lauryl sulfate had a profound effect on post-ionto phoretic skin impedance, considerably amplifying the effect of current passage. Post-iontophoretic impedance spectra of skin pretreated with oleic acid showed a smaller decrease in skin impedance. Neither stear ic acid nor linoleic acid had comparable effects, however. For these e nhancers, the changes observed were attributable to the vehicle, propy lene glycol, which complemented the action of iontophoresis and increa sed its effectiveness. A parameter, analogous to the membrane time con stant, was introduced that enabled the degree of perturbation and the rate of recovery of skin impedance to be gauged. Conclusions: This stu dy provides the first direct in vivo measurements of the interaction b etween chemical and electrical enhancement, the two principal techniqu es used to promote transdermal drug delivery. Changes in the reduction of skin impedance induced by the passage of current have been used as indicators of the interaction between an array of diverse penetration enhancers and iontophoresis. The post-iontophoretic impedance data ha ve been fitted to a circuit model involving the parallel arrangement o f a resistor and a constant-phase element, and the modulation of the e ffect of iontophoresis by the penetration enhancers has been determine d from changes in the equivalent circuit parameter values.