Work

In vitro two stage one compartment dumping test data and absorption/formulation PBBM modeling to explain a bioequivalence failure of valsartan formulations

Year: 2025

Type: article

Abstract: BACKGROUND: In recent years, significant efforts have been made to develop new dissolution methods capable of predicting the in vivo behavior of pharmaceutical formulations. This is essential for establishing valid in vitro-in vivo correlations (IVIVCs) and biopredictive models. However, many of these methodologies involve sophisticated, costly, and complex devices designed to replicate human physiology. The objective of this study was to predict in vivo bioequivalence (BE) using a simplified dynamic dissolution methodology and to establish a physiologically based biopharmaceutics model (PBBM). METHODS: An oral fixed-dose combination of valsartan (VALS, BCS Class IV) and hydrochlorothiazide (HCTZ, BCS Class III) was used for the study. The reference product (Co-Diovan® Forte) and two generic formulations were evaluated using a dissolution approach. A two stage one compartment dissolution technique, known as the "dumping test," was applied to assess drug release profiles. The in vitro dissolution data obtained were incorporated into the PBBM, with two scaling factors-one for time and another for absorption-to enhance predictive accuracy. RESULTS: The "dumping test" successfully simulated the different dissolution behaviors of the formulations and explained the failure of bioequivalence in certain cases. The established IVIVC demonstrated both validity and biopredictive capability. The percentage prediction errors (% PEs) for the PBBM, after incorporating in vitro data and the scaling factors, remained within acceptable regulatory limits. CONCLUSIONS: The study demonstrated that a simple dynamic dissolution methodology can effectively predict in vivo bioequivalence and formulation performance. The application of the "dumping test" provided valuable insights into the dissolution characteristics of different formulations, highlighting its potential as a cost-effective and practical tool for biopredictive studies.

Source: European Journal of Pharmaceutics and Biopharmaceutics

DOI: 10.1016/j.ejpb.2025.114932

Authors: Bárbara Sánchez-Dengra, Alejandro Ruiz-Picazo, Isabel Gonzalez-Alvarez, Marta Gonzalez-Alvarez, Marival Bermejo

Institution: Universitat de Miguel Hernández d'Elx

Language: English

Topic: Drug Solubulity and Delivery Systems

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,210