Development and Optimization of Fast-Dissolving Oral Films Containing Metformin HCl and Curcumin–β-Cyclodextrin Inclusion Complex Using a Box–Behnken Design

Abstract

The aim of this study was to develop and optimize rapidly dissolving oral films containing metformin HCl and curcumin-β-cyclodextrin (β-CD) inclusion complexes. Curcumin complexes were prepared in molar ratios of 1:1, 1:2, and 1:3, and characterization studies (FTIR, DSC, and solubility testing) confirmed successful complex formation. The 1:2 molar ratio demonstrated the greatest improvement in aqueous solubility. Oral films were prepared using HPMC E5 and chitosan as film-forming polymers and glycerin, polysorbate 80, and citric acid as supporting excipients. A Box-Behnken design was employed to evaluate the effects of polymer ratio, plasticizer (glycerin) level, and casting thickness on disintegration time, tensile strength, and surface pH. All formulations demonstrated acceptable homogeneity, physiologically compatible surface pH values, and consistent drug content. Response surface analysis revealed that both polymer ratio and film thickness significantly affected disintegration time and mechanical strength, while surface pH was not significantly affected by formulation variables. The optimized film consisted of a 2.5 HPMC E5:chitosan ratio, 15% plasticizer, and a cast thickness of 180 µm, with a desirability value of 1,000. Overall, the developed films demonstrate strong potential as a rapid-release oral delivery platform supported by improved curcumin solubility and robust formulation optimization.