Vonoprazan Fumarate

Vonoprazan is new potential gastric acid suppression agent, and it is classified as potassium-competitive acid blocker (P-CAB). Potassium-competitive acid blocker, which is different from PPI, enters parietal cell canaliculus in an active form, is stable in an acidic environment, and does not require acid activation. Protonated P-CAB will make non-covalent bonds with H+/K+-ATPase, thus inactivating the H+/K+-ATPase with a slower dissociation rate and for a longer time.

Fig. 1 The mode of action of proton pump inhibitors (PPIs) and Vonoprazan against H. pylori infection. (Miftahussurur M, et al. 2020)

Vonoprazan fumarate (VPF) is a novel potassium-competitive acid blocker with potential applications in the management of acid-related diseases and Helicobacter pylori (H. pylori) eradication. However, the poor solubility and low bioavailability of VPF impede its therapeutic efficacy. To address these challenges, researchers developed amorphous solid dispersion (ASD)-loaded orodispersible films (ODFs). VPF ASDs were prepared with hydroxypropyl methylcellulose (HPMC K4M), polyethylene glycol 4000, and Poloxamer 407 using a melt-based approach. The optimized VPF ASD, showing the best dissolution, was formulated at a 1: 6 drug-to-polymer ratio with HPMC K4M and followed the Higuchi-diffusion kinetic model. The ASD was subsequently loaded into ODFs prepared by solvent casting using different polymers, and ODF7 (75 mg polyvinyl alcohol) exhibited the fastest disintegration, least moisture uptake, and 100% drug release in 10 minutes. The in vivo pharmacokinetic studies in rabbits showed a 2.2-fold increase in relative bioavailability (221.98%) compared to commercial tablets and palatability. These results support the use of VPF-ASD-loaded ODFs as a suitable approach for the enhancement of solubility, stability, and systemic exposure, as well as patient compliance.

Fig. 2 SEM of pure VPF and VPF-HPMC-ASD. (El-Shenawy A A, Abd Elkarim R A. 2026)