Jean Louis Mesens

Transdermal Permeation of Alniditan by Iontophoresis: In Vitro Optimization and Human Pharmacokinetic Data

AbstractPurpose. The aim of this paper was to assess the feasibility of electrically enhanced transdermal delivery of alniditan, a novel 5 HT1D agonist for the treatment of migraine. Methods. An in vitro study was first performed to optimize the different parameters affecting iontophoresis efficiency. The mechanism of alniditan permeation by iontophoresis was investigated. Finally, a phase I clinical trial was performed to assess systemic delivery of alniditan by iontophoresis. Results. i) In vitro: The optimal conditions were found with a buffer like ethanolamine at a pH of 9.5, with Ag/AgCl electrodes and a direct current application. Alniditan permeation was enhanced when increasing the current density, the duration of current application and the drug concentration. Iontophoresis slightly increased drug quantities in stratum corneum compared to passive diffusion but it strongly increased alniditan quantities in viable skin, ii) The objective to deliver in vivo 0.5 mg of alniditan within less than 1 h was reached but an erythema was detected at the anode. Conclusions. This study demonstrates the feasibility of iontophoretic delivery system for antimigraine compounds.

Transdermal alniditan delivery by skin electroporation

The aim of this study was to evaluate the transdermal permeation of alniditan by electroporation and to compare with iontophoretic delivery. The influence of the electrical parameters of electroporation was investigated in vitro using a factorial design study. The transdermal flux of alniditan was enhanced by two orders of magnitude by application of high voltage electrical pulses. The electrical parameters of electroporation-i.e. the voltage, the duration and the number of pulses-allowed a control of drug permeation. Both transport during and after pulsing were shown to be important for alniditan transdermal delivery by electroporation. Electroporation was found more efficient in promoting alniditan permeation than an iontophoresis transferring the same amount of charges.

General CommentaryA Tribute to Dr. Marcus E. Brewster: October 14, 1957–September 15, 2014

1 Drug Delivery & Disposition, KU Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium 2 Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland 3 Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, United Kingdom 4 Department of Pharmaceutics, University of Florida, Gainesville, Florida 32610 5 Department of Drug Product Development, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium

A Tribute to Dr. Marcus E. Brewster: October 14, 1957–September 15, 2014

1 Drug Delivery & Disposition, KU Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium 2 Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland 3 Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, United Kingdom 4 Department of Pharmaceutics, University of Florida, Gainesville, Florida 32610 5 Department of Drug Product Development, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium