ArticleThe AAPS journal2011
Utility of physiologically based absorption modeling in implementing Quality by Design in drug development.
Article in The AAPS journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Assessment of In Vivo Clinical Product Performance of a Weak Basic Drug by Integration of In Vitro Dissolution Tests and Physiologically Based Absorption Modeling.The AAPS journal · 2015Trial
- Utility of physiologically based modeling and preclinical in vitro/in vivo data to mitigate positive food effect in a BCS class 2 compound.AAPS PharmSciTech · 2013Trial
- Comprehensive design and characterization of pH-gradient-loaded donkey-milk exosomes for oral octreotide delivery: A bench-to-in silico roadmap.International journal of pharmaceutics · 2026Article
- Utilizing Physiologically Based Pharmacokinetic Modeling and Virtual Simulation for Simvastatin Tablets to Evaluate the Sensitivity of Using Parent vs Metabolite as Analyte on Bioequivalence Assessment.The AAPS journal · 2025Article
- Conformational Landscape, Polymorphism, and Solid Forms Design of Bicalutamide: A Review.Molecules (Basel, Switzerland) · 2025Review
- 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
- The Future of Medicine: AI and ML Driven Drug Discovery Advancements.Current topics in medicinal chemistry · 2025Review
- Establishment of Biopredictive Dissolution and Bioequivalence Safe Space Using the Physiologically Based Biopharmaceutics Modeling for Tacrolimus Extended-Release Capsules.AAPS PharmSciTech · 2024Article
- Article
- Review
- Regulatory utility of physiologically based pharmacokinetic modeling for assessing food impact in bioequivalence studies: A workshop summary report.CPT: pharmacometrics & systems pharmacology · 2023Review
- Current State and Challenges of Physiologically Based Biopharmaceutics Modeling (PBBM) in Oral Drug Product Development.Pharmaceutical research · 2023Review
- Why Do Dietary Flavonoids Have a Promising Effect as Enhancers of Anthracyclines? Hydroxyl Substituents, Bioavailability and Biological Activity.International journal of molecular sciences · 2022Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- The Use of Physiologically Based Pharmacokinetic Analyses-in Biopharmaceutics Applications -Regulatory and Industry Perspectives.Pharmaceutical research · 2022Review
- In Silico Modeling and Simulation to Guide Bioequivalence Testing for Oral Drugs in a Virtual Population.Clinical pharmacokinetics · 2021Review
- Physiologically-based pharmacokinetics modeling to investigate formulation factors influencing the generic substitution of dabigatran etexilate.CPT: pharmacometrics & systems pharmacology · 2021Article
- Biopharmaceutics Applications of Physiologically Based Pharmacokinetic Absorption Modeling and Simulation in Regulatory Submissions to the U.S. Food and Drug Administration for New Drugs.The AAPS journal · 2021Article
- Pharmacokinetics of the CYP3A4 and CYP2B6 Inducer Carbamazepine and Its Drug-Drug Interaction Potential: A Physiologically Based Pharmacokinetic Modeling Approach.Pharmaceutics · 2021Article
- Well-tempered MCMC simulations for population pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To implement Quality by Design (QbD) in drug development, scientists need tools that link drug products properties to in vivo performance. Physiologically based absorption models are potentially useful tools; yet, their utility of QbD implementation has not been discussed or explored much in the literature. We simulated pharmacokinetics (PK) of carbamazepine (CBZ) after administration of four oral formulations, immediate-release (IR) suspension, IR tablet, extended-release (XR) tablet and capsule, under fasted and fed conditions and presented a general diagram of a modeling and simulation strategy integrated with pharmaceutical development. We obtained PK parameters and absorption scale factors (ASFs) by deconvolution of the PK data for IR suspension under fasted condition. The model was validated for other PK profiles of IR formulations and used to predict PK for XR formulations. We explored three key areas where a modeling and simulation approach impacts QbD. First, the model was used to help identify optimal in vitro dissolution conditions for XR formulations. Second, identification of critical formulations variables was illustrated by a parameter sensitivity analysis of mean particle radius for the IR tablet that showed a PK shift with decreased particle radius, C (max) was increased and T (max) was decreased. Finally, virtual trial simulations allowed incorporation of inter-subject variability in the model. Virtual bioequivalence studies performed for two test formulations suggested that an in vitro dissolution test may be a more sensitive discriminative method than in vivo PK studies. In summary, a well-validated predictive model is a potentially useful tool for QbD implementation in drug development.
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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.