Physiologically based absorption modeling to predict bioequivalence of controlled release and immediate release oral products

Mitra, Amitava; Petek, Boštjan; Bajc, Aleksander; Velagapudi, Raja; Legen, Igor

doi:10.1016/j.ejpb.2018.11.019

Cited by 21 publications

(22 citation statements)

References 22 publications

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“…Mitra et al investigated the reliability of GastroPlus™ and the PKPlus™ module to simulate plasma concentration vs. time profiles for drugs of classes I and II [44]. The prediction for both classes closely matched the observed data, claiming that PK parameters were predicted accurately.…”

Section: Gastroplus™mentioning

confidence: 94%

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Al-Tabakha

Alomar

2020

Pharmaceutics

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Purpose: To review in vitro testing and simulation platforms that are in current use to predict in vivo performances of generic products as well as other situations to provide evidence for biowaiver and support drug formulations development. Methods: Pubmed and Google Scholar databases were used to review published literature over the past 10 years. The terms used were “simulation AND bioequivalence” and “modeling AND bioequivalence” in the title field of databases, followed by screening, and then reviewing. Results: A total of 22 research papers were reviewed. Computer simulation using software such as GastroPlus™, PK-Sim® and SimCyp® find applications in drug modeling. Considering the wide use of optimization for in silico predictions to fit observed data, a careful review of publications is required to validate the reliability of these platforms. For immediate release (IR) drug products belonging to the Biopharmaceutics Classification System (BCS) classes I and III, difference factor (ƒ1) and similarity factor (ƒ2) are calculated from the in vitro dissolution data of drug formulations to support biowaiver; however, this method can be more discriminatory and may not be useful for all dissolution profiles. Conclusions: Computer simulation platforms need to improve their mechanistic physiologically based pharmacokinetic (PBPK) modeling, and if prospectively validated within a small percentage of error from the observed clinical data, they can be valuable tools in bioequivalence (BE) testing and formulation development.

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Section: Gastroplus™mentioning

confidence: 94%

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Al-Tabakha

Alomar

2020

Pharmaceutics

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“…There are two ways in which intraindividual variability can be incorporated into the PBPK‐based VBE trials. The first option is simply to attribute intraindividual variability obtained from a previous replicated clinical study to the predicted BE metrics post hoc (Mitra et al., 2019). This is a pragmatic approach that lacks mechanistic understanding of changes in the system components between two different occasions.…”

Section: Current Scientific Considerations For Supporting Bcs III Drug Waiver and Modeling Bcs Iii Drug Absorptionmentioning

confidence: 99%

Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help

Cristofoletti

Zhao

et al. 2021

Biopharm & Drug Disp

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The 2017 Guidance by U.S. Food and Drug Administration (FDA) has recommended the criteria to qualify for a Biopharmaceutical Classification System (BCS)-based biowaiver that includes high solubility of the drug across the physiological pH range as well as the formulation considerations, e.g., being qualitatively the same and quantitatively very similar to the reference product. These were ratified by the International Council for Harmonization (ICH) in 2018. The FDA has used the similar verbiage when referring to the BCS-based biowaiver option for BCS class III drugs (highly soluble but poorly permeable). However, establishing in vitro-in vivo correlations (IVIVC) using conventional mass balance deconvolution approaches, which assumes a single absorption compartment, is not likely for very rapidly dissolving dosage forms containing BCS III drugs. Unlike conventional mass balance deconvolution techniques, physiologically based pharmacokinetic models are able to disentangle different processes contributing to the input function, e.g., dissolution, gastrointestinal transit, and permeation and to establish IVIVC using variants of the compartmental absorption and transit model, supporting biowaiver for formulations containing BCS III drugs. However, there are knowledge gaps that need to be filled.This review provides a systematic assessment of the advancements in applications of physiologically based pharmacokinetic (PBPK) models for IVIVC and biowaiver for such cases with the aim of identifying the most important gaps and hurdles. It concludes by calling for research efforts on the impact of excipients on dissolution and permeation, alongside the development of PBPK modeling to link these in vitro characteristics to in vivo bioequivalence outcomes through simulations of virtual clinical studies

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“…Dr. Fang also stated that model‐based bioequivalence (BE) approaches are essential to the development of complex generic LAI products, enabling abbreviated new drug application applicants to conduct BE studies efficiently 16–18 . The modeling approaches can help applicants evaluate the study design and sensitivity quantitatively, as well as maximize the information gained from efficient BE studies.…”

Section: Model‐informed Drug Development For Long‐acting Injectable Pmentioning

confidence: 99%

“…Fang also stated that model-based bioequivalence (BE) approaches are essential to the development of complex generic LAI products, enabling abbreviated new drug application applicants to conduct BE studies efficiently. [16][17][18] The modeling approaches can help applicants evaluate the study design and sensitivity quantitatively, as well as maximize the information gained from efficient BE studies. In designing adequately powered PK BE studies, the applicant can conduct virtual BE study simulations comparing alternative designs (such as optimal BE study design) based on the prior PK information of the reference product.…”

Section: Model-informed Drug Development For Long-acting Injectable Pmentioning

confidence: 99%

Model‐Informed Drug Development for Long‐Acting Injectable Products: Summary of American College of Clinical Pharmacology Symposium

Sharan

Fang

Lukáčová

et al. 2021

Clinical Pharm in Drug Dev

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Physiologically based absorption modeling to predict bioequivalence of controlled release and immediate release oral products

Cited by 21 publications

References 22 publications

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help

Model‐Informed Drug Development for Long‐Acting Injectable Products: Summary of American College of Clinical Pharmacology Symposium

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