A physiologically-based drug absorption modeling for orally disintegrating tablets.
Atorvastatin
In silico modeling and simulation
In vitro biorelevant dissolution
Oral drug absorption
Orally disintegrating tablets
Orodispersible tablets
Pharmacokinetics
Journal
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
29
02
2020
revised:
26
04
2020
accepted:
26
04
2020
pubmed:
7
5
2020
medline:
7
2
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
The aim of this research was to simulate oral pharmacokinetic (PK) profiles of atorvastatin from orally disintegrating tablets (ODTs) dosed without water ingestion in fasted humans. The in vitro dissolution profiles of three different formulations of ODTs were evaluated with fasted state biorelevant media using a paddle dissolution apparatus, and the results were coupled with an in silico model to simulate the in vivo oral PK profiles of ODTs following administration to humans. Since the dissolution rates of the ODTs in the intestinal medium (FaSSIF-V2) were highly affected by pre-exposure of the tablets to the stomach medium (FaSSGF), the simulation model took account of the relationship between the gastric emptying time and the dissolution performance of the tablets in the small intestine. The ODTs were formulated with drug-containing pellets. After oral dosing of the ODTs without water ingestion, gastric emptying of the pellets was assumed to follow first order kinetics. Thus, rate constants ranging between 0.69 and 8.3 h
Identifiants
pubmed: 32371153
pii: S0939-6411(20)30115-6
doi: 10.1016/j.ejpb.2020.04.018
pii:
doi:
Substances chimiques
Tablets
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-9Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.