An in vitro method for studying the iontophoretic enhancement of drug transport through skin

Abstract

An electrodiffusion cell and measurement system has been developed to study the factors governing the transport of ionized drugs through skin under the influence of an electric field. The system allows the determination of transport rates in vitro under conditions of either constant current or constant voltage across the skin. Both accelerating and retarding voltages may be applied. To test the method, the iontophoretic transport of a negatively charged bone resorption agent, etidronate disodium (ethanehydroxydiphosphonate, EHDP) was measured across excised human skin. An enhancement factor of 50-70 over passive diffusion was obtained using a constant current density of 140 μA-cm −2, and a factor of approximately 100 was obtained with a constant applied voltage of -0.5 V. At the lowest power levels tested (14 μA-cm −2 or -0.25 V) the enhancements were in reasonable agreement with the predictions of a constant field model for electrodiffusion; however, at higher power levels a phenomenological parameter, the drug transference number in the membrane, appeared to be more useful. Neither the constant current nor the constant voltage mode was found to be a completely satisfactory way of controlling drug delivery in this model. A current-voltage regimen in which both parameters are varied may be required in order to achieve consistent results.