Optimization and Formulation Design of Gels of Diclofenac and Curcumin for Transdermal Drug Delivery by Box-Behnken Statistical Design

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. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:580-593, 2011