Favaron, A;
Hens, B;
Montanha, M;
McAllister, M;
Tomaszewska, I;
Moustafa, S;
Alvarenga de Oliveira, M;
... Orlu, M; + view all
(2024)
Can in vitro/in silico tools improve colonic concentration estimations for oral extended-release formulations? A case study with upadacitinib.
Journal of Controlled Release
, 370
pp. 182-194.
10.1016/j.jconrel.2024.04.024.
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Abstract
Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution. A series of in vitro dissolution experiments were gathered using the USP Apparatus I, III and IV in presence of biorelevant media, simulating both fasted and fed state conditions. A key outcome from the current study was to establish an in vitro-in vivo correlation (IVIVC) between (i) the dissolution profiles obtained from the USP I, III and IV methods and (ii) the fraction absorbed of drug as deconvoluted from the plasma concentration-time profile of the drug. When linking the fraction dissolved as measured in the USP IV model, a Level A IVIVC was established. Moreover, when using the different dissolution profiles as input for PBPK modeling, it was also observed that predictions for plasma Cmax and AUC were most accurate for USP IV compared to the other models (based on predicted versus observed ratios). Furthermore, the PBPK model has the utility to extract the predicted concentrations at the level of the colon which can be of utmost interest when working with specific in vitro assays.
| Type: | Article |
|---|---|
| Title: | Can in vitro/in silico tools improve colonic concentration estimations for oral extended-release formulations? A case study with upadacitinib |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jconrel.2024.04.024 |
| Publisher version: | https://doi.org/10.1016/j.jconrel.2024.04.024 |
| Language: | English |
| Additional information: | Copyright © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Colonic targeting, Oral drug delivery, Rinvoq, Upadacitinib, Modeling, Dissolution |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191372 |
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