An In Vitro–In Vivo Simulation Approach for the Prediction of Bioequivalence

Vlachou, Marilena; Karalis, Vangelis

doi:10.3390/ma14030555

Cited by 9 publications

(10 citation statements)

References 55 publications

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“…The analysis started by estimating the PK variables of hydrochlorothiazide, donepezil, and amlodipine according to the strategy shown in Figure 1 . The C-t data used in this study were generated using the PK models and model parameters reported in the literature [ 21 , 22 , 23 , 24 , 25 , 26 ]. For each drug, two-sequence, two-period, 2 × 2 crossover BE studies in 100 virtual subjects were generated.…”

Section: Resultsmentioning

confidence: 99%

An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence

Karalis

2023

Pharmaceuticals

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In bioequivalence, the maximum plasma concentration (Cmax) is traditionally used as a metric for the absorption rate, despite the fact that there are several concerns. The idea of “average slope” (AS) was recently introduced as an alternative metric to reflect absorption rate. This study aims to further extend the previous findings and apply an in silico approach to investigate the kinetic sensitivity of AS and Cmax. This computational analysis was applied to the C-t data of hydrochlorothiazide, donepezil, and amlodipine, which exhibit different absorption kinetics. Principal component analysis (PCA) was applied to uncover the relationships between all bioequivalence metrics. Monte Carlo simulations of bioequivalence trials were performed to investigate sensitivity. The appropriate programming codes were written in Python for the PCA and in MATLAB® for the simulations. The PCA verified the desired properties of AS and the unsuitability of Cmax to reflect absorption rate. The Monte Carlo simulations showed that AS is quite sensitive to detecting differences in absorption rate, while Cmax has almost negligible sensitivity. Cmax fails to reflect absorption rate, and its use in bioequivalence gives only a false impression. AS has the appropriate units, is easily calculated, exhibits high sensitivity, and has the desired properties of absorption rate.

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Section: Resultsmentioning

confidence: 99%

An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence

Karalis

2023

Pharmaceuticals

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“…In silico mathematical modeling and simulation are valuable tools in the early stage of drug development for optimizing the design dosage form. This method uses software to input model data including the in vitro data of the drug and simulates the data to predict the pharmacokinetic profile [6]. The application of computer simulation recently involved in analyzing about physiologically based pharmacokinetic (PBPK) models, predicting the pharmacokinetics profile of certain drugs (e.g, inhalers), and predict bioequivalence using virtual subjects [5,[7][8][9].…”

Section: Resultsmentioning

confidence: 99%

“…Vlacho and Karalis were developing a novel in vitro in vivo simulation (IVIVS) approach for a new generic amlodipine/irbesartan/hydrochlorothiazide combination products and programming in MATLAB®. This approach allows for predicting the probability of success in bioequivalence studies [6]. Another several platforms also have been applicated by other researchers such as Stella® Professional, B 2 O simulator and PK-Sim® which may not being applied as much as compared to the previously mentioned.…”

Section: The Other In Silico Platformmentioning

confidence: 99%

Application in silico Modeling Simulation in Bioequivalence Studies: A Review

Pawestri

2023

J. Food Pharm. Sci

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Bioequivalence testing aims to ensure that the therapeutic performance of the drug is consistent and reproducible when it is administrated. Modeling and simulation in silico methods are currently performed to conduct virtual bioequivalence studies. Various computer simulation software is used to generate the simulation and model input data. This review summarizes the software used for predicting in vivo performance which supports the analysis of virtual bioequivalence testing. GastroPlus™ and SimCyp® are widely used platforms in generating data for virtual bioequivalence studies. The studies suggest that the validity procedure is necessary for modeling and simulation. The in silico method has become a valuable tool in bioequivalence studies as supporting extension of the biowaiver drug list and contributing to future drug development.

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“…Therefore, assessment of the impact of variations in dissolution conditions and the consequence of the in-vivo performance of the drug can be predicted from this model. Thus it can help the research and development group in the translation of in-vitro and in-vivo data at the early stage of drug development 38 .…”

Section: Physiologically Based Pharmacokinetic (Pbpk) Modelingmentioning

confidence: 99%

A Brief Review on Pharmaceutical Dissolution Interlinking the Aspects of Science and Regulation

Rangarao¹,

Monica²,

Bhattacharyya³

2022

Bulletin of Pharmaceutical Sciences. Assiut

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Dissolution is a multistep process describes the affinity of the solute and the solvent by which a solid substance interacts among the heterogeneous phases of solute -solute, solventsolvent, and the solute-solvent interface to yield a solution. In the pharmaceutical industry dissolution testing of solid dosage form gives a signal of the operability of the dosage form in the biological system. The rate of absorption is partially or completely controlled by the dissolution of the drug from its dosage forms in the gastrointestinal tract. Dissolution, the vital quality control aspects, also ensure batch-to-batch uniformity in drug release, bioavailability, and the development of efficacious therapeutic dosage forms. It also ensures the evaluation of their critical biopharmaceutical parameters. Hence the study of dissolution is an interplay between the science and the development of the regulatory profile of a dosage form for quality control aspects. The present review focuses on the science, factors relevant to in-vitro dissolution, and therefore the role of its in pharmaceutical regulation.

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An In Vitro–In Vivo Simulation Approach for the Prediction of Bioequivalence

Cited by 9 publications

References 55 publications

An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence

An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence

Application in silico Modeling Simulation in Bioequivalence Studies: A Review

A Brief Review on Pharmaceutical Dissolution Interlinking the Aspects of Science and Regulation

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