Article ; Online: Using molecularly dissolved drug concentrations in PBBMs improves the prediction of oral absorption from supersaturating formulations.
2024 Volume 194, Page(s) 106703
Abstract: Predicting the absorption of drugs from enabling formulations is still challenging due to the limited capabilities of standard physiologically based biopharmaceutics models (PBBMs) to capture complex absorption processes. Amongst others, it is often ... ...
Abstract | Predicting the absorption of drugs from enabling formulations is still challenging due to the limited capabilities of standard physiologically based biopharmaceutics models (PBBMs) to capture complex absorption processes. Amongst others, it is often assumed that both, molecularly and apparently dissolved drug in the gastrointestinal lumen are prone to absorption. A recently introduced method for measuring concentrations of molecularly dissolved drug in a dynamic in vitro dissolution setup using microdialysis has opened new opportunities to test this hypothesis and refine mechanistic PBBM approaches. In the present study, we compared results of PBBMs that used either molecularly or apparently dissolved concentrations in the simulated gastrointestinal lumen as input parameters. The in vitro dissolution data from three supersaturating formulations of Posaconazole (PCZ) were used as model input. The modeling outcome was verified using PCZ concentration vs. time profiles measured in human intestinal aspirates and in the blood plasma. When using apparently dissolved drug concentrations (i.e., the sum of colloid-associated and molecularly dissolved drug) the simulated systemic plasma exposures were overpredicted, most pronouncedly with the ASD-based tablet. However, if the concentrations of molecularly dissolved drug were used as input values, the PBBM resulted in accurate prediction of systemic exposures for all three PCZ formulations. The present study impressively demonstrated the value of considering molecularly dissolved drug concentrations as input value for PBBMs of supersaturating drug formulations. |
---|---|
MeSH term(s) | Humans ; Biopharmaceutics/methods ; Solubility ; Administration, Oral ; Colloids ; Intestinal Absorption/physiology ; Models, Biological |
Chemical Substances | Colloids |
Language | English |
Publishing date | 2024-01-14 |
Publishing country | Netherlands |
Document type | Journal Article |
ZDB-ID | 1154366-8 |
ISSN | 1879-0720 ; 0928-0987 |
ISSN (online) | 1879-0720 |
ISSN | 0928-0987 |
DOI | 10.1016/j.ejps.2024.106703 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 3705: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.