title: A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions.
abstract: OBJECTIVE
  The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions.
  
  
  METHODS
  Two model drug compounds were studied in TIM-1: a lyophilized Lactobacillus strain and paracetamol (acetaminophen). The Lactobacillus survival rate was determined by bacterial counting in the gastric and ileal effluents while simulating the conditions of the gastrointestinal tract of infants or adults. The availability for absorption of paracetamol from two oral dosage forms was investigated by measuring the drug concentration in jejunal dialysis fluid. The effect of gastrointestinal passage time and food intake on paracetamol absorption was also studied.
  
  
  RESULTS
  The Lactobacillus survival rate in both gastric and ileal effluents was higher during simulation of the infant compared to adult conditions. We also showed that (i) paracetamol absorption was faster when it was administered as a free powder than in sustained-release tablet form, (ii) a slow passage time resulted in a delay in the absorption of paracetamol, and (iii) there was a lower rate of absorption when paracetamol was ingested with a standard breakfast as opposed to water. The in vitro results were consistent with in vivo data, showing the predictive value of TIM-1.
  
  
  CONCLUSIONS
  TIM-1 is a powerful tool for supplying valuable information about the effects of various gastrointestinal conditions on biopharmaceutical behavior and efficacy of drug delivery systems in the development of oral formulations.
authors.affiliation: Equipe de Recherche Technologique Conception, Ingénierie et Développement de l'Aliment et du Médicament, Centre de Recherche en Nutrition Humaine d'Auvergne, Faculté de Pharmacie, Université d'Auvergne, 63001 Clermont-Ferrand, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blanquet
authors.forename: Evelijn
authors.initials: E
authors.lastname: Zeijdner
authors.forename: Erick
authors.initials: E
authors.lastname: Beyssac
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Meunier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Denis
authors.forename: Robert
authors.initials: R
authors.lastname: Havenaar
authors.forename: Monique
authors.initials: M
authors.lastname: Alric
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000284:Administration, Oral; D004064:Digestive System / Q000187:drug effects*; D004304:Dosage Forms; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology*; D008954:Models, Biological; D011237:Predictive Value of Tests
chemical_list: D004304:Dosage Forms; D000082:Acetaminophen