Exploring the structure-permeation relationship of topical tricyclic antidepressants used for skin analgesia

Publication date: 15 May 2017 Source:International Journal of Pharmaceutics, Volume 523, Issue 1 Author(s): Kuo-Sheng Liu, Tse-Hung Huang, Ibrahim A. Aljuffali, En-Li Chen, Jhi-Joung Wang, Jia-You Fang The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay. Cutaneous tolerance to TCAs was assessed using nude mouse skin. The skin deposition increased following the increase of lipophilicity after excluding the effect of solubility, with clomipramine exhibiting the highest skin retention. A contrary result was observed for TCA penetration into the receptor. Of the permeants tested, clomipramine demonstrated the best skin-targeting ability. Nortriptyline and clomipramine demonstrated selective uptake into the hair follicles, exhibiting a 2.5-fold higher follicular accumulation than desipramine. Replacement of nitrogen with carbon in the seven-member ring increased skin absorption. The tertiary amine TCAs demonstrated higher absorption than the...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research