The relationship between hydrogen-bonded ion-pair stability and transdermal penetration of lornoxicam with organic amines

Abstract

Ion pair is an effective chemical approach to enhance skin penetration of drugs. The aim of this work was to investigate the skin enhancement mechanism of ion pairs for lornoxicam (LOX) with organic amines from the standpoint of ion-pair stability. Various organic amines, triethylamine (TEtA), diethylamine (DEtA), N-(2'-hydroxyethanol)-piperdine (NP), diethanolamine (DEA) and triethanolamine (TEA), were employed as the counter ions for enhancing LOX across the rabbit skin in vitro. Intermolecular interaction between LOX and organic amines was confirmed by IR and (1)H NMR spectroscopy in solution. All the amines, especially TEtA, provided an obvious enhancing effect for LOX. Spectra data proved that the presence of organic amines led to ion pair formation in solution which was associated with proton transfer of hydroxyl group of LOX. The stability parameter of ion pairs, ion-pair lifetimes (T(life)), was calculated from the NMR data. The results demonstrated that the stability of ion-pair complexes was closely related with the basicity of organic amines and exhibited a great contribution on skin permeation of LOX.