Title
A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions
Author
Blanquet, S.
Zeijdner, E.
Beyssac, E.
Meunier, J.-P.
Denis, S.
Havenaar, R.
Alric, M.
TNO Voeding
Publication year
2004
Abstract
Purpose. 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 (acctaminophen). 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. Chemicals / CAS: pancreatin, 8049-47-6; paracetamol, 103-90-2; pepsin A, 9001-75-6; starch, 9005-25-8, 9005-84-9; triacylglycerol lipase, 9001-62-1; Acetaminophen, 103-90-2; Dosage Forms
Subject
Pharmacology Biology
Physiological Sciences
Dissolution profile
Gastrointestinal model
Oral formulations
Paracetamol
Probiotics
bacilor
bile salt
pancreatin
paracetamol
pepsin A
probiotic agent
starch
triacylglycerol lipase
unclassified drug
article
bacterial survival
bile secretion
body temperature
computer simulation
drug absorption
drug delivery system
drug dosage form
drug formulation
drug solubility
food intake
gastrointestinal tract
gastrointestinal transit
in vitro study
Lactobacillus casei
pancreas secretion
peristalsis
pH
priority journal
salivation
small intestine
stomach
stomach secretion
Acetaminophen
Administration, Oral
Digestive System
Dosage Forms
Gastrointestinal Transit
Models, Biological
Predictive Value of Tests
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http://resolver.tudelft.nl/uuid:00b35cec-dab4-46f9-be1f-1d6099fb0d22
DOI
https://doi.org/10.1023/b:pham.0000022404.70478.4b
TNO identifier
237682
ISSN
0724-8741
Source
Pharmaceutical Research, 21 (4), 585-591
Document type
article