TRANSDERMAL DELIVERY OF CYCLOSPORINE-A USING ELECTROPORATION

Topical delivery of cyclosporin A (CSA) is desirable for treating psor iasis, but it is hindered by the barrier property of stratum corneum, and the physicochemical properties of CSA. Attempts to deliver CSA fro m a solution prepared in 40% ethanol (EtOH) in phosphate buffered sali ne (PBS) using iontophoresis did not result in any significant increas e in drug delivery, compared to passive. However, the use of electropo ration pulses as a physical penetration enhancer enabled delivery of a significant amount of CSA. Single pulse electroporation study indicat ed that the amount of EtOH delivered across the skin increased as the applied electrode voltage (U-electrode) was increased. However, it did not translate into a proportional increase in the delivery of CSA and only a three to four times increase, compared to passive delivery, wa s seen with the single pulse electroporation. The drug contact duratio n had a varying effect in the efficiency of transdermal delivery of CS A. Four hour contact duration was chosen for the multiple pulse study. Use of multiple pulses (25 pulses, 10 ms each) at U-electrode 200 V r esulted in a sixty-fold increase, compared to passive, in the delivery of CSA to the skin. Transdermally delivered CSA was mostly bound to t he skin and only a small amount was seen to cross the full skin into t he receiver compartment. In a study of solvent transport, the flux of water was up to three times larger than that of EtOH after electropora tion. (C) 1998 Elsevier Science B.V.