Kostantini, Christina, Spilioti, Evanthia, Bevernage, Jan, Ceulemans, Jens, Hansmann, Simone, Hellemans, Katleen, Jede3, Christian, Kourentas, Alexandros, Reggane, Maude, Shah, Lipa, Wagner, Christian, Reppas, Christos and Vertzoni, Maria (2023) Usefulness of the BioGIT system in screening for differences in early exposure in the fasted state on an a priori basis. International journal of pharmaceutics. ISSN 03785173

Abstract

The main objective of the present study was to confirm the usefulness of BioGIT data in the evaluation of the impact of dose and/or formulation on early exposure after administration of immediate release (IR) or enabling drug products of low solubility active pharmaceutical ingredients (APIs) with a glass of water in the fasted state. BioGIT experiments were performed with four APIs: Compound Α (tablet, three dose levels), Compound E (capsule PiC1, capsule PiC2 and tablet), fenofibrate (Lipidil® capsule and Lipidil 145 ONE® tablet) and bedaquiline (HP-β-CD aqueous solution and tablet). Based on mean plasma AUC0-60min values which became available after completion of the BioGIT experiments, mean BioGIT AUC0-50min values were useful for the evaluation of the impact of dose and/or formulation on early exposure. Furthermore, the log-transformed mean BioGIT AUC0-50min ratios of two doses and/or two formulations calculated from data collected in this study and in a recent study with two diclofenac potassium products (Cataflam® tablet and Voltfast® sachet, same dose) (n=7 pairs of ratios), and the corresponding log-transformed mean plasma AUC0-60min ratios calculated from clinical data were included in a previously established correlation between log-transformed mean plasma AUC0–60min ratios with log-transformed mean BioGIT AUC0–50min ratios (n=9 pairs of ratios). The correlation between log-transformed plasma AUC0–60min ratios vs. log-transformed BioGIT AUC0–50min ratios was confirmed (n=16 pairs of ratios, R=0.90). Compared with the previously established correlation the statistical characteristics were improved. Based on this study, the BioGIT system could be useful as a screening tool for assessing the impact of dose and/or formulation differences on early exposure, after administration of immediate release or enabling drug products with a glass of water in the fasted state, on an a priori basis.

Item Type:	Article
Keywords:	BioGIT; early exposure; correlation; enabling formulations; weak bases
Date Deposited:	21 Feb 2023 00:45
Last Modified:	21 Feb 2023 00:45
URI:	https://oak.novartis.com/id/eprint/48490