Fabrication and In-Vitro/In-Vivo Characterization of Orodispersible Films Loaded with Amorphous Solid Dispersion of Vonoprazan Fumarate

Abstract

Purpose: Vonoprazan fumarate (VPF) is a novel potassium-competitive acid blocker with promising therapeutic potential for acid related disorders and as an adjunct to Helicobacter pylori eradication, yet its clinical utility is limited by poor solubility and low bioavailability. Here, we explore the development of amorphous solid dispersion (ASD)-loaded orodispersible films (ODFs) to overcome these barriers. Methods: ASDs of VPF were prepared and characterized using hydroxypropyl methylcellulose (HPMC K4M), polyethylene glycol 4000, and Poloxamer 407. ODFs were fabricated by solvent-casting with sodium carboxymethyl cellulose, HPMC K4M, and polyvinyl alcohol (PVA) as film-forming polymers, incorporating glycerin as a plasticizer. Various parameters as weight and thickness variation, in-vitro drug release, disintegration time, moisture uptake, and in-vivo pharmacokinetic parameters were investigated. Results: VPF ASDs were achieved the optimal dissolution at a 1:6 (w/w) drug-to-polymer (HPMC K4M) ratio with Higuchi-diffusion kinetics. Stability studies confirmed VPF integrity in the ASD form. Among the ODF formulations, ODF7 (contains 75 mg PVA) demonstrated superior performance with rapid disintegration, lowest moisture uptake, and maximum drug release within 10 min. In-vivo pharmacokinetic evaluation in rabbits revealed a 2.2-fold increase in relative bioavailability (221.98%) compared to the VPF marketed tablet, while palatability testing confirmed its acceptability. Conclusion: These findings demonstrate the potential of VPF-ASD-loaded ODFs as a viable approach to enhance drug solubility, stability, and systemic exposure.