Optimization and Evaluation of Colchicine Patch Formulation Based on Box-Behnken Design.

Abstract

This study aimed to optimize colchicine (COL) transdermal patches to enhance key quality attributes, including adhesion, drug release, and transdermal penetration. The goal was to develop a formulation with improved performance based on BOX-Behnken Design (BBD) optimization. The BBD method was used to design experiments evaluating the effects of three key variables: COL content, penetration enhancer content (azone and propylene glycol), and the solvent evaporation time at 80 °C. A total of 17 randomized experiments were conducted. Patches were assessed for initial adhesion force, peel strength, drug release in vitro for 48 h, and transdermal penetration using texture analysis, in vitro release testing (IVRT), and in vitro permeation testing (IVPT). Fourier-Transform Infrared Spectroscopy (FT-IR) was employed to check for interactions between formulation components, and stability was evaluated under accelerated storage conditions. The optimized formulation included 9.8% COL, 5% azone, and 5% propylene glycol, with evaporation performed for 23 min at 80 °C. This formulation achieved an adhesion index close to the predicted value. In vitro drug release and transdermal permeation pattern for 48 h followed the Weibull equation, with measured cumulative release of 27.62 mg and cumulative penetration per unit area of 256.34 µg/cm², confirming the effectiveness of the optimization. FT-IR analysis showed no significant interactions among components, and accelerated stability testing demonstrated the formulation's robustness over time. The use of BBD for formulation optimization resulted in a transdermal system of COL, highlighting its suitability for avoiding the side effects associated with oral colchicine.