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Updated: Jan 2, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
In vitro-In vivo Relationship and Bioequivalence Prediction for Modified-Release Capsules Based on a PBPK Absorption
Rebeka Jereb1, Jerneja Opara2, Igor Legen2
1Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia. rebeka.jereb@ffa.uni-lj.si.
Abstract:
A physiologically based pharmacokinetic (PBPK) absorption model was developed in GastroPlus™ based on data on intravenous, immediate-release (IR), and modified-release (MR) drug products. The predictability of the model was evaluated by comparing predicted and observed plasma concentration profiles; average prediction errors (PE) were below 10%. IVIVR was developed using mechanistic deconvolution for a MR drug product to evaluate the in vivo effect of a proposed change in dissolution specification. The predictability of the IVIVR was evaluated and PE were below 10%; however, external validation was not possible due to the lack of data. The developed PBPK absorption model and IVIVR were used to predict plasma concentration profiles and pharmacokinetic (PK) parameters for a hypothetical formulation with 0% of drug dissolved in 2 h in in vitro dissolution test. Both methods predicted the insignificant effect of a change in in vitro dissolution profile on in vivo product performance. The bioequivalence of a hypothetical formulation to the test product was evaluated using virtual clinical trial. The performed analysis supported the proposed change in dissolution specification. A validated PBPK absorption model was proposed as an adequate alternative to IVIVC, when IVIVC could not have been developed according to the guidelines.
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