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

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• 作者：Niketkumar Patel¹ ; Shashank Jain² ; Senshang Lin ; ^{linse@stjohns.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Transdermal iontophoresis ; Alzheimer&rsquo ; s disease ; Tacrine hydrochloride ; In vitro-in vivo correlation ; WinNonlin
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：393-403
• 全文大小：637 K

文摘

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 0.1–0.3 mA current strength and tacrine concentration loading of 5–20 mg/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 0.2 mA current application. In vivo studies confirmed current and concentration dependent tacrine plasma profiles with possible tacrine depot formation under the skin in-line with earlier in vitro results. Correlation of in vivo transdermal absorption rates to in vitro permeation profiles revealed higher in vitro permeation fluxes compare to in vivo transdermal absorption rates at varied combination of current strength and concentrations. Present in vivo studies support the earlier published in vitro findings and tacrine plasma profiles show a potential to reach therapeutic effective concentration of tacrine hydrochloride to provide a platform for pre-programmed tacrine delivery.