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Screening for Differences in Early Exposure in the Fasted State with in Vitro Methodologies can be Challenging: Experience with the BioGIT System.

Authors :
Kostantini C
Spilioti E
Bevernage J
Ceulemans J
Hansmann S
Hellemans K
Jede C
Kourentas A
Reggane M
Shah L
Wagner C
Vertzoni M
Reppas C
Source :
Journal of pharmaceutical sciences [J Pharm Sci] 2023 Aug; Vol. 112 (8), pp. 2240-2248. Date of Electronic Publication: 2023 Mar 12.
Publication Year :
2023

Abstract

The Biorelevant Gastrointestinal Transfer (BioGIT) system is a useful screening tool for assessing the impact of dose and/or formulation on early exposure after administration of immediate release or enabling drug products with a glass of water in the fasted state. The objective of this study was to investigate potential limitations. BioGIT experiments were performed with five low solubility active pharmaceutical ingredients with weakly alkaline characteristics: mebendazole (tablet and chewable tablet), Compound E (aqueous solutions, three doses), pazopanib-HCl (Votrientâ„¢ tablet, crushed Votrientâ„¢ tablet and aqueous suspension), Compound B-diHCl (hard gelatin capsule, three doses) and Compound C (hard gelatin capsule containing nanosized drug and hard gelatin capsule containing micronized drug). For all formulation or dose comparisons the ratio of mean BioGIT AUC <subscript>0-50</subscript>   <subscript>min</subscript> values was not predictive of the ratio of mean plasma AUC <subscript>0-60</subscript>   <subscript>min</subscript> values which became available after completion of BioGIT experiments. BioGIT experimental conditions have not been designed to simulate the gastrointestinal drug transfer process after administration of chewable tablets or aqueous solutions, therefore, BioGIT may not be useful for the assessment of intraluminal performance early after administration of such drug products. Also, based on this study, BioGIT may not be useful in investigating the impact of dose and/or formulation on early exposure when the dose is not administered with a glass of water to fasted healthy individuals or when BioGIT data are highly variable. Finally, the rapid dissolution of nanocrystals after administration of low solubility weak bases may require adjustment of the pH in the gastric compartment of BioGIT to slightly higher pH values. Limitations identified in this study for the BioGIT system may be also relevant to other in vitro systems proposed for similar evaluations.<br />Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest.<br /> (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1520-6017
Volume :
112
Issue :
8
Database :
MEDLINE
Journal :
Journal of pharmaceutical sciences
Publication Type :
Academic Journal
Accession number :
36918113
Full Text :
https://doi.org/10.1016/j.xphs.2023.03.004