The Permeation of Nalmefene Hydrochloride across Different Regions of Ovine Nasal Mucosa

Abstract

Nasal drug delivery has been generating widespread interest in the drug delivery field because it could not only be used in local treatment but also in systemic administration. Various properties of nasal drug delivery made it an alternative route for intravenous and oral administration, such as bypassing of enzymatic or acidic degradation and exempting the first-pass hepatic metabolism; the relatively large epithelial surface, porous endothelial membranes and highly vascularized epithelium also maintained the rapid absorption of drugs.Various factors that might affect the permeability of drugs through the nasal mucosa could be broadly classified into three categories as follow: biological factors, formulation aspects and device-related factors. 1,2) The nasal structure feature was one of the main biological factors. The nasal cavity could be anatomically segregated into five different regions: nasal vestibule, atrium, respiratory area, olfactory region and nasopharnyx.2) The structure features of different regions were quite different which resulted in different blood supply, nasal secretion and mucociliary clearance among them, 3) and thus may influence the permeability of drug and presystemic degradation. Moreover, different devices and dosage forms may result in differences of the deposition place and residence time of drugs in the nasal cavity. Therefore, the research on the permeability of drug through mucosas of different regions of nasal cavity in vitro may help us to find out the main absorption region of drugs and understand the mechanism, rate and extent of drug absorption across the nasal mucosa. Furthermore, it may also be helpful for choosing dosage forms to deposit drugs on the main absorption region and prolong the residence time.However, there were few studies about the permeation of drugs through mucosas of different regions of the nasal cavity. In present study, the Valia-Chien chamber technique 4) and a hydrophilic model drug nalmefene hydrochloride [17-N-cyclopropylmethyl-3,14-b-dihydroxy-4,5-a-epoxy-6-methylene morphinan hydrochloride] 5) which was chosen for its possibility to be developed as a product for emergency medicine, 6) was used to study the permeability of the five different regions. The permeability coefficient and accumulative drug permeation was investigated. The permeation of NH through different pieces obtained from the same middle turbinate mucosa and the same septum mucosa was also investigated to evaluate the uniformity of such mucosa.The excised tissue of animals such as sheep, 7-9) pig, 10,11) rabbit, 4,12,13) and ox 14,15) had been employed by researchers to study the drug delivery through nasal mucosa. Among these animals, the morphology of the ovine mucosa is more comparable to that of humans because of the presence of ciliated and non ciliated cells, basal cells, goblet cells and serous glands. 16) In the present study, ovine nasal mucosa was employed. During the experimental process, it was easier to handle the tissue and keep the mucosa intact and unstrained. Ther...

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