Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
J Pharm Sci. 2011 Feb;100(2):580-93. doi: 10.1002/jps.22292.
The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release.
本研究旨在开发和优化双氯芬酸二乙胺（DDEA）和姜黄素（CRM）的透皮凝胶制剂。采用 3 因素 3 水平 Box-Behnken 设计，推导出二阶多项式方程，构建响应预测的等高线图。研究的自变量为聚合物浓度（X(1)）、乙醇（X(2)）和丙二醇（X(3)），每个因素的水平分别为低、中、高。研究的因变量为 DDEA 的皮肤渗透速率（Y(1)）、CRM 的皮肤渗透速率（Y(2)）和凝胶的粘度（Y(3)）。绘制响应面图，建立多项式的统计学有效性，以找到优化制剂的组成，使用 Franz 型扩散池进行评估。DDEA 的渗透速率与乙醇浓度成正比增加，但与聚合物浓度成反比降低，而 CRM 的渗透速率与聚合物浓度成正比增加。凝胶对 DDEA 和 CRM 分别显示出非 Fickian 超 II 级（典型零级）和非 Fickian 扩散释放机制。该设计展示了推导的多项式方程和等高线图在预测依赖变量值方面的作用，用于透皮药物释放的凝胶制剂的制备和优化。
