Development and Evaluation of Curcumin-Loaded Mucoadhesive Buccal Films Using Green Deep Eutectic Solvents via Design of Experiments

<b>Background/Objectives:</b> This study aimed to develop and formulation-design curcumin-loaded buccal films using a green deep eutectic solvent (DES) to improve drug solubility and support localized mucosal delivery, with the help of a Design of Experiments (DoE) approach. <b>Methods:</b> Various DESs with different components and molar ratios were prepared, characterized, and the optimal DES was selected. Curcumin-loaded buccal films were prepared by solvent casting, employing the optimal DES as the solvent system. A three-factor and five-level central composite design was applied to <b>s</b>ystematically investigate the amounts of HPMC K100, Kollicoat^® IR, and DES in buccal films, and mucoadhesive strength, elongation (%), swelling index, swelling time, and thickness were identified as critical responses. Based on these responses, characterization, in vitro release, ex vivo permeation, and in vitro biological activity studies were performed on the model-predicted optimal formulations. <b>Results:</b> Choline chloride: propylene glycol (1:4 molar ratio) was selected as the optimal DES due to its viscosity, pH, organoleptic properties, and the highest curcumin solubility (11.90 ± 0.15 mg/mL). While DES increased curcumin solubility, buccal films were successfully obtained. Six formulations identified through model-based DoE optimization were advanced to detailed experimental evaluation. The drug release exhibited sustained curcumin release profiles over 24 h, and ex vivo studies showed <2% mucosal permeation. The lead formulations demonstrated in vitro cell compatibility, anti-inflammatory and antioxidant activities, and enhanced wound-healing-related bioactivity. <b>Conclusions:</b> Curcumin-loaded buccal films containing DES and developed using a DoE-guided formulation strategy successfully demonstrated the acceptable formulation properties and screening-level in vitro biological activities, offering a promising formulation platform for localized buccal delivery applications.