Box-Behnken Design Assisted Optimization and Characterization of Chitosan Film for Simultaneous Topical Delivery of Ascorbic Acid and Metronidazole.

The objective of this study was to develop chitosan films plasticized with glycerol for the topical delivery of ascorbic acid and metronidazole. The films were prepared using a casting technique in which an aqueous ascorbic acid solution served as the solvent, eliminating the need for additional mineral or organic acids. The influence of compositions on film characteristics-specifically mechanical properties and surface pH-was examined, and an optimized formulation was identified using a Box-Behnken design-response surface methodology. Relevant characterization techniques and in vitro evaluations were conducted to assess the properties and performance of the optimized film formulation. Results showed that both glycerol and ascorbic acid contributed to the plasticization of the films. Fourier-transform infrared spectroscopic analysis of the optimized film revealed the formation of chitosan ascorbate and interactions between chitosan and glycerol. In addition, the thermogram and powder X-ray diffractogram demonstrated alterations in the thermal behavior and crystallinity of the embedded bioactive compounds. The developed film possessed the preferred swelling capacity. Moreover, in vitro release studies revealed a co-release pattern, delivering both bioactive compounds simultaneously. These findings suggest that the prepared chitosan-based film could serve as a promising platform for topical delivery.