Τίτλος:
The effect of reduced gastric acid secretion on the gastrointestinal disposition of a ritonavir amorphous solid dispersion in fasted healthy volunteers: an in vivo - in vitro investigation.
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
This paper summarizes efforts to (i) better understand the behavior of amorphous solid dispersions (ASDs) under real-life dosing conditions and (ii) evaluate the capability of in vitro methodologies to capture gastro-intestinal drug disposition. In a first part of the study, five healthy volunteers participated in a two-way crossover trial in which one Norvir® tablet (100 mg ritonavir) was dosed under fasted and fasted + PPI conditions. Gastrointestinal aspirates were collected from both the stomach and duodenum as a function of time to map the gastrointestinal drug disposition of the ritonavir ASD formulation and to evaluate the impact of reduced gastric acid secretion on formulation performance. In both test conditions, ritonavir was shown to supersaturate in the upper GI tract illustrating the capacity of the formulation strategy itself to generate supersaturated drug content. In parallel, in vivo test conditions were closely mimicked in a multitude of in vitro methodologies (i.e., USP II dissolution apparatus, BioGIT and TIM-1 system) with the aim to evaluate their ability to predict in vivo gastrointestinal drug disposition. The selected in vitro methodologies were found capable of qualitatively and/or quantitatively picking up trends observed in the intraluminal sampling study. © 2020 Elsevier B.V.
Συγγραφείς:
Van Den Abeele, J.
Kostantini, C.
Barker, R.
Kourentas, A.
Mann, J.C.
Vertzoni, M.
Beato, S.
Reppas, C.
Tack, J.
Augustijns, P.
Περιοδικό:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Λέξεις-κλειδιά:
ritonavir, adult; area under the curve; Article; aspiration; crossover procedure; dispersion; dissolution; drug absorption; drug disposition; drug solubility; duodenum; fasting; female; human; human experiment; in vitro study; in vivo study; male; maximum concentration; normal human; priority journal; stomach; stomach acid secretion; tablet formulation; time to maximum plasma concentration
DOI:
10.1016/j.ejps.2020.105377
