Mechanistic studies of flux variability of neutral and ionic permeants during constant current dc iontophoresis with human epidermal membrane

Effects of electrophoresis and electroosmosis during alternating current iontophoresis across human epidermal membrane

“…2) indicate that electroosmosis induced by the AC electric fields was negligible. This finding is consistent with previous studies of HEM under different AC conditions7,13,14 and in agreement with DC studies of HEM that electroosmosis contributes ∼10% of iontophoretic transport for small monovalent ionic permeants (i.e., the effect of electroosmosis is ∼10% of the effect of electrophoresis) 8,9. In a previous study with synthetic Nuclepore membranes,17 significant flux enhancement of ARA was observed under the same AC conditions used in the present study.…”

“…Pe is the Peclet number that characterizes the effect of convective solvent flow and can be expressed as8,20: where Δ x is the effective thickness of the membrane. The convective solvent flow velocity and Pe are linearly proportional to the applied electric field 2,9. For a neutral permeant, the enhancement factor E ΔΨ can be expressed as8,20: Pe can be calculated from the enhancement factor of the neutral permeant in the experiments with eq.…”

“…It may follow from this that electric field‐induced alterations of the effective pore size of skin during constant current DC transdermal iontophoresis may be responsible for variability in the flux of drug molecules due to different extents of size exclusion of the drug molecule and the background electrolyte ions in the pores 8. Also, the fluxes of drug molecules could be affected by possible alteration of the pore charge density of skin under the applied electric field during iontophoresis 7,9. Another potential problem with DC iontophoresis is the alteration of the electrochemical environment in the solution surrounding the electrodes, which can induce electrochemical burns of the skin if an inappropriate electrode design is used 10–12…”

Effects of alternating current frequency and permeation enhancers upon human epidermal membrane

“…AC at high frequency also has higher threshold of sensation and threshold of “let-go” than DC (Dalziel and Mansfield, 1950; Dalziel and Massoglia, 1956; Okabe et al, 1986) giving better safety profiles and allowing the use of higher electric current in transdermal iontophoretic transport. Another advantage of AC is that DC iontophoresis can alter the electrochemical environment of the solution surrounding the electrodes (Li et al, 2004). Skin electrochemical burns may occur as a result of such solution changes during long iontophoresis application or when an inappropriate electrode design is used.…”

“…Flux variability has been observed during conventional constant direct current (DC) iontophoresis in vitro (Green et al, 1991; Delgado-Charro and Guy, 1994; Singh et al, 1995; Zhu et al, 2002) and in vivo (Meyer et al, 1988; Li et al, 2003). This variability is related to the time dependent alterations of the pore pathways in skin that can occur during conventional constant current DC iontophoresis (Li et al, 2004). AC is more effective in sustaining a constant state of pore induction in HEM, and constant skin resistance AC iontophoresis has been shown to have less transdermal iontophoretic flux variability for neutral permeants than conventional DC (Zhu et al, 2002).…”