Drug Permeation through Skin Is Inversely Correlated with Carrier Gel Rigidity

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• 作者：Duc-Viet Nguyen ; Fang Li ; Hairui Li ; Bin Sheng Wong ; Chang Yee Low ; Xiang-Yang Liu ; Lifeng Kang
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：February 2, 2015
• 年：2015
• 卷：12
• 期：2
• 页码：444-452
• 全文大小：540K
• ISSN：1543-8392

文摘

Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e., low molecular weight gelling agent N-lauroyl-l-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel鈥搒kin interface; as a result, the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, and thus, the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a 鈥渦niversal鈥?power law regardless of the gel types, i.e., 1/J = 1/J<sub>0sub> + a(G*)<sup>蔚sup>/C<sub>0sub> with a = 11.25, 蔚 = 0.21 卤 0.03 for GP-1 gels, and a = 0.16, 蔚 = 1.05 卤 0.06 for Carbopol gels, J<sub>0sub> is the steady flux without gel (G* = 0), and C<sub>0sub> is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.