Betahistine Orodispersible Tablets Provide Faster Onset, Higher Absorption, and Improved Bioavailability Compared with Conventional Tablets: An Integrated Dissolution–Permeation Study

Background Betahistine is widely used in the symptomatic treatment of vestibular vertigo and Ménière-related disorders, and therapeutic benefit depends on how rapidly effective drug levels become available after administration. Conventional tablets rely on gastric disintegration and dissolution prior to absorption. Orodispersible tablets (ODTs) disperse in the oral cavity and may enable earlier drug uptake and improved systemic availability. This study investigated whether a betahistine ODT provides faster drug availability, greater absorption, and improved bioavailability-related performance compared with a conventional tablet using a mechanistic in vitro evaluation. Methods Betahistine ODT and conventional immediate-release tablets containing the same labeled dose were evaluated in a sequential physiological model. Oral cavity performance was assessed in artificial saliva by measuring disintegration time, wetting behavior, and early drug release during the first 15 minutes. A two-stage gastric-to-intestinal pH transition model was applied to determine the fraction of drug remaining dissolved and immediately available for absorption. Pre-gastric uptake was evaluated using porcine buccal mucosa mounted in Franz diffusion cells by measuring drug transport across the tissue over time. Intestinal epithelial transfer was examined using polarized epithelial monolayers, and cumulative drug transport was quantified. Plasma protein binding and drug stability were evaluated in saliva, gastric, and intestinal media to exclude differences related to degradation or binding. Results The ODT disintegrated rapidly in artificial saliva (24.8 ± 6.1 s) compared with the conventional tablet (412 ± 95 s, p < 0.001). Rapid dispersion produced markedly faster release; within 10 minutes 82.7 ± 6.4% of the dose was released from the ODT versus 21.5 ± 7.2% from the conventional tablet (p < 0.001). After transition to intestinal conditions, the dissolved fraction available for absorption at 30 minutes was 88.5 ± 7.2% for the ODT and 54.2 ± 9.8% for the conventional tablet (p < 0.001). Buccal permeation was substantially higher with the ODT, showing greater flux (8.1 ± 1.4 vs 2.7 ± 0.9 μg/cm²/h, p < 0.001) and shorter lag time (12.4 ± 4.2 vs 28.7 ± 6.8 min, p < 0.001). Intestinal epithelial permeability was similar between formulations; however, cumulative transported drug at 120 minutes was greater for the ODT (486 ± 88 ng vs 312 ± 74 ng, p = 0.004). Plasma protein binding and chemical stability were comparable in all media. Conclusion Betahistine orodispersible tablets produced immediate oral dispersion, a larger early dissolved fraction, and earlier mucosal uptake, resulting in greater epithelial transfer despite unchanged intrinsic permeability. The findings demonstrate faster drug availability, enhanced absorption, and improved bioavailability-related performance compared with conventional tablets. Reduced gastric residence and partial pre-gastric uptake further suggest a potential improvement in gastrointestinal tolerability together with a faster onset of therapeutic action.