Mechanistic studies of the transdermal iontophoretic delivery of 5-OH-DPAT in vitro.

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 (Flux(ss)) 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 10 mM in the donor phase, resulted in a 2.5-fold enhancement of the Flux(ss). The Flux(ss) 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 Flux(ss) of 5-OH-DPAT, explained by a reduced electroosmotic flow and an increased counter-ion flow. Optimization of the conditions resulted in a maximum Flux(ss) of 5-OH-DPAT of 1.0 micromol x cm(-2) h(-1) demonstrating the potential of the iontophoretic delivery of this dopamine agonist for the symptomatic treatment of Parkinson's disease.

• Authors: Oliver W Ackaert, Jeroen Van Smeden, Jeroen De Graan, Durk Dijkstra, Meindert Danhof, Joke A Bouwstra
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 99 Issue 1 Pg. 275-85 (Jan 2010) ISSN: 1520-6017 [Electronic] United States
• PMID: 19718740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Acetaminophen
• 5-hydroxy-2-N,N-dipropylaminotetralin
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)
• Acetaminophen (administration & dosage, chemistry, pharmacokinetics)
• Administration, Cutaneous
• Antiparkinson Agents (administration & dosage, chemistry, pharmacokinetics)
• Electroosmosis
• Humans
• In Vitro Techniques
• Iontophoresis
• Skin (metabolism)
• Skin Absorption
• Solubility