Development of a novel rabeprazole modified release formulation to reduce the dosing frequency: A trial and triumph with physiologically based biopharmaceutics modeling.

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Bioequivalence achieved (specific ratios not provided in abstract)

• Primary Outcome: Bioequivalence of once-daily modified-release rabeprazole versus twice-daily delayed-release reference formulation

• Nnt Or Sensitivity: Bioequivalence ratios showed good agreement between predicted and observed values

• Confidence Interval: Not reported in abstract

Clinical Application

High feasibility if formulation receives regulatory approval; once-daily dosing improves practical implementation Relevant to Australian practice where rabeprazole is PBS-listed; TGA would require bioequivalence data for generic approval; aligns with RACGP emphasis on medication adherence Adult patients requiring proton pump inhibitor therapy, particularly those with compliance challenges on twice-daily regimens

Abstract

Advanced in silico tools, such as physiologically based biopharmaceutics models (PBBM) and physiologically based pharmacokinetic models (PBPK), play a pivotal role in model-informed formulation development (MIFD). In the present study, these methodologies were utilized in the development of a novel rabeprazole modified-release (MR) formulation for improved patient compliance by reducing the dosing frequency relative to existing delayed-release (DR) formulation. A MR formulation containing combination of delayed release and pulsatile release components was designed based on the hypothetical dissolution targets. A PBBM was first established using literature-derived clinical data and used to simulate the performance of formulations with varied dissolution profiles. Initial MR formulation prototypes (once a day) were evaluated in pilot-1 bioequivalence (BE) study against reference formulation (twice a day) but results indicated infra bioequivalence outcome. After pilot-1 study, the formulation and the dissolution method were optimized and then model was refined to predict the pilot 1 outcomes. The validated model was then employed to select suitable pilot-2 prototypes and to prospectively predict their BE outcomes under fasted and fed conditions. The predicted BE ratios were in good agreement with the observed pilot-2 study results. Therefore, the same model was used to make prospective predictions with increased subjects to understand the in vivo performance of pivotal test formulation and lead to the successful bioequivalence outcome, product commercialization, ultimately aiding in increased patient compliance. This work highlights the value of a model-informed strategy in accelerating formulation optimization, reducing development timelines and costs, and strengthening decision-making within pharmaceutical development programs.

References

1. 1.Maddukuri, H., Boddu, R., Chaudhari, S. M., Choudhury, A. A., Kambam, V., Khan, S. M., Naidu, V. R., Singh, S. K., Saini, A. K., & Kollipara, S. (2026). Development of a novel rabeprazole modified release formulation to reduce the dosing frequency: A trial and triumph with physiologically based biopharmaceutics modeling. Journal of Pharmacokinetics and Pharmacodynamics. https://doi.org/10.7324/JAPS.2025.231215