ArticleAAPS PharmSciTech2024
A Semi-Mechanistic Physiologically Based Biopharmaceutics Model to Describe Complex and Saturable Absorption of Metformin: Justification of Dissolution Specifications for Extended Release Formulation.
Article in AAPS PharmSciTech, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Application of New Approach Methodologies to Improve Oral Biopharmaceutic Assessments.Pharmaceutics · 2026Review
- Evaluation of USP 3 Apparatus to Develop Biopredictive Fasted and Fed Dissolution Methods for Extended-Release Desvenlafaxine Succinate Tablets.ACS omega · 2026Article
- Leveraging Model Integrated Bioequivalence (MIBE) to Address Regulatory Concerns and Waive Repeat Bioequivalence Studies-A Case Study with Clopidogrel.Journal of clinical pharmacology · 2026Article
- Development of in vitro-in vivo correlation for establishing patient-centric quality standards of dissolution for lamotrigine extended-release tablets.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2025Article
- Virtual Bioequivalence Assessment and Dissolution Safe Space Exploration for Fixed-Dose Metformin-Glyburide Tablet Using Physiologically Based Biopharmaceutics Modeling.Pharmaceutics · 2025Article
- Considering Opportunities and Challenges When Implementing the Model Master File Framework - a Meeting Report.Pharmaceutical research · 2025Article
- Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation.AAPS PharmSciTech · 2025Review
- Physiologically Based Biopharmaceutics Modeling Coupled with Biopredictive Dissolution in Development of Bioequivalent Formulation for Mesalamine Enteric Coated Tablet: A Tough Nut to Crack.AAPS PharmSciTech · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
Physiologically based pharmacokinetic (PBPK) or physiologically based biopharmaceutics models (PBBM) demonstrated plethora of applications in both new drugs and generic product development. Justification of dissolution specifications and establishment of dissolution safe space is an important application of such modeling approaches. In case of molecules exhibiting saturable absorption behavior, justification of dissolution specifications requires development of a model that incorporates effects of transporters is critical to simulate in vivo scenario. In the present case, we have developed a semi-mechanistic PBBM to describe the non-linearity of BCS class III molecule metformin for justification of dissolution specifications of extended release formulation at strengths 500 mg and 1000 mg. Semi-mechanistic PBBM was built using physicochemical properties, dissolution and non-linearity was accounted through incorporation of multiple transporter kinetics at absorption level. The model was extensively validated using literature reported intravenous, oral (immediate & extended release) formulations and further validated using in-house bioequivalence data in fasting and fed conditions. Virtual dissolution profiles at lower and upper specifications were generated to justify the dissolution specifications. The model predicted literature as well as in-house clinical study data with acceptable prediction errors. Further, virtual bioequivalence trials predicted the bioequivalence outcome that matched with clinical study data. The model predicted bioequivalence when lower and upper specifications were compared against pivotal test formulations thereby justifying dissolution specifications. Overall, complex and saturable absorption pathway of metformin was successfully simulated and this work resulted in regulatory acceptance of dissolution specifications which has ability to reduce multiple dissolution testing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.