TRANSDERMAL DELIVERY OF FENTANYL BY ELECTROPORATION .2. MECHANISMS INVOLVED IN DRUG TRANSPORT

Purpose. The aim of the present report was to systematically analyze t he mechanisms involved in fentanyl transdermal transport by skin elect roporation. Methods. The study was performed in vitro with full-thickn ess hairless mt skin, skin electroporation being carried out with five exponentially-decaying pulses of 100 V applied voltage and around 600 ms pulse duration. Results. Transport during and after pulsing are bo th important in transdermal delivery of fentanyl by skin electroporati on. Rapid transport occurred during pulsing due to electrophoresis and diffusion through highly permeabilized skin. No electroosmosis was ob served. 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 th e skin with fentanyl and hence rapidly overcame skin barrier. Conclusi ons. 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 care ful consideration of formulation variables art: essential for the deve lopment and optimization of drug delivery by skin electroporation.