In vitro permeation of several model drugs across rabbit nasal mucosa

Abstract

The objectives in the present study were to establish a useful in vitro experimental method for detailed understanding of the nasal absorption of several drugs and its enhancement. Nasal mucosa was excised from the nasal septum in rabbits and mounted in a Ussing-type diffusion chamber. Firstly, the electrophysiological parameters, transmucosal potential difference, short-circuit current, and transmucosal electrical resistance ( R m) were measured to determine the mucosal viability. Viability was maintained over at least 6 h after mounting the mucosa in the chamber. Secondly, the in vitro membrane permeability of several model drugs was measured using the diffusion chamber. Disodium cromoglycate, fluorescein isothiocyanate-dextran (FD) of different molecular weights (4400, 9400, 35 600 and 71 200), and propranolol hydrochloride were chosen as model drugs. The membrane permeation profile showed a typical pseudo steady-state curve with a short lag time, and the permeability coefficient cm/s) of these model drugs was calculated to be 3.428 × 10 −6, 1.275 × 10 −6, 0.677 × 10 −6, 0.181 × 10 −6, 0.126 × 10 −6 and 2.554 × 10 −5, respectively. Thirdly, the effects of several permeation enhancers on the membrane permeation of FD (Mol. Wt 9400) as well as the electrophysiological parameters were evaluated. Four bile salts, namely, sodium glycocholate, sodium taurocholate, sodium deoxycholate (DC) and sodium taurodihydrofusidate (STDHF), were selected as permeation enhancers. Each enhancer rapidly reduced the R m value, and hence increased the mucosal permeability of FD. The enhancing effect of DC and STDHF on FD permeation was greater than that of other two. This experimental method using the Ussing type diffusion chamber appears to be a useful tool for understanding the nasal absorption of drugs and the mechanism of absorption enhancment.