Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport

The aim of the present report was to systematically analyze the mechanisms involved in fentanyl transdermal transport by skin electroporation. The study was performed in vitro with full-thickness hairless rat skin, skin electroporation being carried out with five exponentially-decaying pulses of 100 V applied voltage and around 600 ms pulse duration. Transport during and after pulsing are both important in transdermal delivery of fentanyl by skin electroporation. Rapid transport occurred during pulsing due to electrophoresis and diffusion through highly permeabilized skin. No electroosmosis was observed. The slow post-pulse passive transport was explained by lasting changes in skin permeability. Measurements of fentanyl quantities in the skin demonstrated that pulses rapidly loaded the viable part of the skin with fentanyl and hence rapidly overcame skin barrier. The different contributions of the transport mechanisms appear to depend on the physicochemical parameters of the transported molecule as well as the solution, suggesting that mechanistic analysis and careful consideration of formulation variables are essential for the development and optimization of drug delivery by skin electroporation.