Transdermal iontophoretic delivery of tacrine hydrochloride: Correlation between in vitro permeation and in vivo performance in rats

Publication date: 20 November 2016 Source:International Journal of Pharmaceutics, Volume 513, Issues 1–2 Author(s): Niketkumar Patel, Shashank Jain, Senshang Lin The aim of present investigation is to evaluate the feasibility of transdermal iontophoretic delivery of tacrine hydrochloride in Sprague Dawley (SD) rats using anodal iontophoretic patches and to correlate plasma tacrine concentration profiles to in vitro tacrine permeation flux. In vitro skin permeation studies were carried out across artificial membrane CELGRAD® 2400, freshly excised SD rat abdominal skin, freshly excised hairless rat abdominal skin, and frozen pig skin to examine the role of permeation membranes. Furthermore, plasma profiles with an application of 0.1–0.3mA current strength and tacrine concentration loading of 5–20mg/ml were obtained in SD rats. The tacrine plasma profiles were fitted to one-compartmental model using WinNonlin and in vivo transdermal absorption rates were then correlated to in vitro permeation profiles using various approaches. Tacrine permeation across membranes revealed current dependent interspecies differences at lower current strength application which diminished at higher current strength application, whereas, no significant difference in tacrine permeation was observed across fresh and frozen SD rat skin under 0.2mA current application. In vivo studies confirmed current and concentration dependent tacrine plasma profiles with possible tacrine depot formation un...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research