Transdermal iontophoretic delivery of a novel series of dopamine agonists in vitro: physicochemical considerations
Article first published online: 10 JUN 2010
© 2010 The Authors Journal compilation © 2010 Royal Pharmaceutical Society of Great Britain
Journal of Pharmacy and Pharmacology
Special Issue: Recent advances in transdermal drug delivery
Volume 62, Issue 6, pages 709–720, June 2010
How to Cite
Ackaert, O. W., De Graan, J., Capancioni, R., Dijkstra, D., Danhof, M. and Bouwstra, J. A. (2010), Transdermal iontophoretic delivery of a novel series of dopamine agonists in vitro: physicochemical considerations. Journal of Pharmacy and Pharmacology, 62: 709–720. doi: 10.1211/jpp.62.06.0007
- Issue published online: 10 JUN 2010
- Article first published online: 10 JUN 2010
- Received October 29, 2009Accepted January 11, 2010
- dopamine agonists;
- transport pathway
Objectives The transdermal iontophoretic delivery of a novel series of 2- aminotetralins and chromanamine-based dopamine agonists was investigated in vitro.
Methods Systematic structural modifications allowed us to investigate their effect on solubility in the donor phase and iontophoretic delivery across human skin. Transport profiles were analysed with nonlinear mixed effect modelling, utilizing an extension to an existing compartmental model. Furthermore, relationships between physicochemical properties and transport parameters were addressed.
Key findings A solubility increase was observed: 5,6-di-OH-DPAT < 5-OH-MPAT < 5-OH-EPAT < 8-OH-DPAC. The structure significantly affected the iontophoretic delivery across human stratum corneum and dermatomed human skin with the highest flux for 5-OH-EPAT and 5-OH-MPAT. The extended model with two skin release constants (KR1, KR2) described more adequately iontophoretic transport profiles than the existing model with one release constant. The extended model suggested two parallel transport pathways during current application. Across human stratum corneum, the electrophoretic mobility, measured with capillary electrophoresis, showed a linear relationship with the electromigrative flux and the zero-order iontophoretic mass input into the skin (I0).
Conclusions Combining transport parameters (I0, KR1 and KR2), predicted from physicochemical properties, with compartmental modelling provided a powerful tool to simulate iontophoretic transport profiles for screening potential candidates and designing experiments.