Next Article in Journal
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions
Next Article in Special Issue
Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro–In Silico Approach
Previous Article in Journal
Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective?
Previous Article in Special Issue
Novel Polymorph of Favipiravir—An Antiviral Medication
Article

On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet

1
Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria
2
Simcyp Division, Certara UK Limited, Level 2-Acero, Sheffield S1 2BJ, UK
3
Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary
4
Galapagos, Analytical Development CMC, Generaal De Wittelaan L11 A3, 2800 Mechelen, Belgium
5
Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria
6
Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Luisa Di Marzio
Pharmaceutics 2021, 13(2), 283; https://doi.org/10.3390/pharmaceutics13020283
Received: 23 January 2021 / Revised: 10 February 2021 / Accepted: 12 February 2021 / Published: 20 February 2021
The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro–in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with those from the PBPK model. The outcome from both models pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions. View Full-Text
Keywords: in vitro–in vivo correlation; physiologically based pharmacokinetic model; BCS Class II; Rivaroxaban; Xarelto; food effect; population kinetics in vitro–in vivo correlation; physiologically based pharmacokinetic model; BCS Class II; Rivaroxaban; Xarelto; food effect; population kinetics
Show Figures

Figure 1

MDPI and ACS Style

Kushwah, V.; Arora, S.; Tamás Katona, M.; Modhave, D.; Fröhlich, E.; Paudel, A. On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet. Pharmaceutics 2021, 13, 283. https://doi.org/10.3390/pharmaceutics13020283

AMA Style

Kushwah V, Arora S, Tamás Katona M, Modhave D, Fröhlich E, Paudel A. On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet. Pharmaceutics. 2021; 13(2):283. https://doi.org/10.3390/pharmaceutics13020283

Chicago/Turabian Style

Kushwah, Varun, Sumit Arora, Miklós Tamás Katona, Dattatray Modhave, Eleonore Fröhlich, and Amrit Paudel. 2021. "On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet" Pharmaceutics 13, no. 2: 283. https://doi.org/10.3390/pharmaceutics13020283

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop