Ion pair formation as a possible mechanism for the enhancement effect of lauric acid on the transdermal permeation of ondansetron.
Transdermal application can be an alternative drug delivery route for ondansetron, an antiemetic drug. Previous studies found that fatty acids, namely oleic and lauric, were the most effective penetration enhancers. The aim of this study was to investigate the formation of an ion pair between ondansetron and lauric acid as a possible mechanism of its enhancing action. Several techniques were used to reveal the formation of an ion pair complex. Partitioning experiments, where the n-octanol/water coefficient was measured, showed an increase in the distribution coefficient in the presence of the acid, possibly as a result of the formation of more lipophilic ion pairs between the charged molecules of ondansetron and lauric acid. Further evidence of complex formation between ondansetron and lauric acid, was gained from the 13C-nuclear magnetic resonance (13C-NMR) spectra of ondansetron, lauric acid, and their mixture (molar ratio 1:1). The NMR spectra revealed alterations to the magnetic environment of the carbon atoms adjacent to the ionized group, which are the carbonyl group of the acid and the nitrogen of the imidazole ring of ondansetron. This evidence substantiates the theory of ion pair formation. Finally, thermal analysis of the binary mixtures of ondansetron and lauric acid revealed the formation of an additional compound, with different melting point from pure ondansetron and lauric acid, which is thermodynamically favored.
Division of Pharmaceutical Technology, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens, Greece.
Dimitrios A
DA
Dimas
Paraskevas P
PP
Dallas
Dimitrios M
DM
Rekkas
D000465:Algorithms; D000932:Antiemetics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004055:Differential Thermal Analysis; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007850:Lauric Acids / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D017294:Ondansetron / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013268:Stimulation, Chemical; D013816:Thermodynamics
D000932:Antiemetics; D007477:Ions; D007850:Lauric Acids; C030358:lauric acid; D017294:Ondansetron