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Development and validation of a new dynamic computer‐controlled model of the human stomach and small intestine
Author(s) -
Guerra Aurélie,
Denis Sylvain,
le Goff Olivier,
Sicardi Vincent,
François Olivier,
Yao AnneFrançoise,
Garrait Ghislain,
Manzi Aimé Pacifique,
Beyssac Eric,
Alric Monique,
BlanquetDiot Stéphanie
Publication year - 2016
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25890
Subject(s) - theophylline , in vivo , digestion (alchemy) , gastric emptying , human stomach , stomach , small intestine , absorption (acoustics) , dosage form , in vitro , chemistry , biomedical engineering , pharmacology , medicine , chromatography , biology , microbiology and biotechnology , biochemistry , materials science , composite material
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.