Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486230 | Journal of Pharmaceutical Sciences | 2010 | 11 Pages |
Abstract
A characterization and optimization of the in vitro transdermal iontophoretic transport of 5-hydroxy-2-(N,N,-di-n-propylamino)tetralin (5-OH-DPAT) is presented. The utility of acetaminophen as a marker of electroosmotic flow was studied as well. The following parameters of iontophoretic transport of 5-OH-DPAT were examined: drug donor concentration, electroosmotic contribution, influence of co-ions, current density, and composition of the acceptor phase. The steady-state flux (Fluxss) of acetaminophen was linearly correlated with the donor concentration and co-iontophoresis of acetaminophen did not influence the iontophoretic flux of 5-OH-DPAT, indicating that acetaminophen is an excellent marker of electroosmotic flow. Lowering the Na+ concentration from 78 to 10âmM in the donor phase, resulted in a 2.5-fold enhancement of the Fluxss. The Fluxss showed a nonlinear relation with the drug donor concentration and an excellent linear correlation with the current density. Reducing the pH of the acceptor phase from 7.4 to 6.2 resulted in a dramatic decrease of the Fluxss of 5-OH-DPAT, explained by a reduced electroosmotic flow and an increased counter-ion flow. Optimization of the conditions resulted in a maximum Fluxss of 5-OH-DPAT of 1.0âµmolâ·âcmâ2âhâ1 demonstrating the potential of the iontophoretic delivery of this dopamine agonist for the symptomatic treatment of Parkinson's disease. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:275-285, 2010
Keywords
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Authors
Oliver W. Ackaert, Jeroen Van Smeden, Jeroen De Graan, Durk Dijkstra, Meindert Danhof, Joke A. Bouwstra,