Enhanced Solubility and Rapid Delivery of Vitamin D3 via Captisol® (β-Cyclodextrin Sulfobutyl Ether) Inclusion Complex in Mouth-Dissolving Films.

Purpose: Vitamin D3 deficiency is a global health concern affecting millions. However, its lipophilicity and poor water solubility limit its pharmaceutical applications. This study aims to improve the solubility of vitamin D3 by forming an inclusion complex with Captisol® (β-cyclodextrin sulfobutyl ether sodium salt) and developing a mouth-dissolving film (MDF) for its delivery. Methods: The inclusion complex was prepared using a green, microwave-assisted method and characterized via molecular docking, phase-solubility studies, drug loading, and FTIR spectroscopy. The optimized complex was incorporated into MDFs which was further evaluated for their physicochemical and mechanical properties and sensory aspects. Results: Molecular docking confirmed a high binding affinity (-10.7 K·mol^-1) between vitamin D3 and Captisol®. The optimum stoichiometric ratio of vitamin D3 and Captisol® was 2:1 confirmed by the solubility curve, drug loading, and FTIR. The complex was incorporated into MDFs prepared using polyvinyl alcohol as a film former and Tween 80 as a plasticizer. The optimized films demonstrated desirable physicochemical and mechanical properties, rapid disintegration (36 s) and dissolution (complete release within the first 5 min), and excellent content uniformity (98.8%). Sensory evaluation revealed high acceptability, although improvements in the film's color and flavor were suggested. Conclusion: This study establishes a novel, eco-friendly approach to enhance the solubility and patient-friendly delivery of vitamin D3.