title: Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine.
abstract: For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer-controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro-in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325-1335. © 2015 Wiley Periodicals, Inc.
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Guerra
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Denis
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: le Goff
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Sicardi
authors.affiliation: Protolab, Clermont Ferrand, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: François
authors.affiliation: UMR 6620 Laboratoire de Mathématiques, Clermont Université, Université Blaise Pascal, Clermont-Ferrand, France.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Yao
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Garrait
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Aimé Pacifique
authors.initials: AP
authors.lastname: Manzi
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Beyssac
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Alric
authors.affiliation: EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France. stephanie.blanquet@udamail.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blanquet-Diot
mesh_terms: D040761:Biomimetic Materials; D003198:Computer Simulation; D004063:Digestion / Q000502:physiology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D007421:Intestine, Small / Q000502:physiology*; D008954:Models, Biological; D013270:Stomach / Q000502:physiology*
keywords: ESIN; bioaccessibility; dynamic gastrointestinal model; immediate and sustained release forms; in vitro/in vivo correlation (IVIVC); pharmaceutical behavior