Dynamic in vitro GastroIntestinal model.
A HIGH-END DISSOLUTION AND DIGESTION APPARATUS "TIM"
The TIM system is used to get reproducible and reliable scientific data about the behavior of your oral drug products during transit through the stomach, the small intestine and large intestine.
This Dynamic in vitro gastro intestinal model is able to mimic the GI conditions of humans in different age groups, like adults, infants and elderly, but also various animal conditions like pigs, calf’s and dogs.
As a reliable in vitro predictive tool, the TIM systems are an alternative to animal studies and help you reduce the failure rate of time-consuming and expensive human clinical studies. The TIM system contributes to an efficient product development by selecting your most promising candidate aimed for selected populations. Studies can be performed under different GI conditions and health status in a fed or fasted state.
A movie is created to explain the dynamics and possibilities of the model, please click right to view.
Please also visit the TIM company website in the NL
- Link to TIM BV -
Application for Pharmaceutical and Formulation Research
● Assessment of BioAccessibility of API
● Optimization of Control release (IR/SR)
● Comparizon of nano or micro API formulations
● Assessment of Drug-Food/Nutrient Interaction
● Stability of API in GI tract.
● Biological Transformation of API by Intestinal Microflora
● Troubleshooting unexpected results in clinical trials
● Evaluation of low permeability and/or low solubility API (BCS 2, 3, 4)
● Evaluation under different physiological conditions, e.g. infants, adults, elderlies, diseases, animals, etc.
"We have reduced our usage and completely closed our dogs facility. Maintaining animal colonies is very expensive, so there’s a big cost saving there. The TIM-1 correctly predicted in vivo rank order in 84% and 79% of cases for AUC and Cmax, respectively…"
Barker et al., J. Pharm. Sci. 103 (11): 3704-3712. doi: 10.1002/jps.24177.
Glaxo Smith Kline
"The use of the TIM1 model in conjunction with GastroPLUS software provides an excellent tool to aid formulation selection based on improved estimates of the in vivo performance of oral dosage delivery formulations."
Naylor et al., Applied Therapeutic Research 6 (1): 15-19
"…examples suggest that the TIM-1 system, which provides an advanced level of control over a dynamic and complex luminal environment, may have several advantages over conventional dissolution methodologies when assessing the performance of dosage forms in either the fasted or fed states."
McAllister et al., Mol. Pharm. 7 (5): 1374-1387.
"Using the more sophisticated TIM-1 model, which is an in vitro model that allows the closest simulation of in vivo dynamic physiological processes occurring in the lumen of the stomach currently available, we confirm that lycopene does not undergo isomerisation in the gastrointestinal tract.."
Richelle et al., Br. J. Nutr. 103: 1800-1807.
Publication → □ Download Publication list ver.Nov2020.
European Journal of Pharmaceutics and Biopharmaceutics. 2020
On the usefulness of compendial setups and tiny TIM system in evaluating the in vivo performance of oral drug products with various release profiles in the fasted state:
Case example sodium salt of A6197.
Schilderink, R., Protopappa, M., Fleth‐James, J., Vertzoni, M., Schaefer, K., Havenaar, R., ... & Reppas, C.
PloS one, 14(4), e0214859. 2019
Survival of Mycobacterium bovis BCG oral vaccine during transit through a dynamic in vitro model simulating the upper gastrointestinal tract of badgers.
Williams, G. A., Koenen, M. E., Havenaar, R., Wheeler, P., Gowtage, S., Lesellier, S., & Chambers, M. A.
European Journal of Pharmaceutics and Biopharmaceutics, 136, 70‐83. 2019
In vitro models for the prediction of in vivo performance of oral dosage forms: Recent progress from partnership through the IMI OrBiTo collaboration.
Butler, J., Hens, B., Vertzoni, M., Brouwers, J., Berben, P., Dressman, J., Andreas, C., Schaefer, K., Mann, J., McAllister, M., Jamei, M., Kostewicz, E., Kesisoglou, E., Langguth, P., Minekus, M., Mullertz, A., Schilderink, R., Koziolek, M., Jedamzik, P., Weitschies, W., Reppas C., Augustijns, P.
Molecular Pharmaceutics, 16 June, 2017
Gastrointestinal and Systemic Disposition of Diclofenac under Fasted and Fed State Conditions Supporting the Evaluation of in Vitro Predictive Tools.
Jens Van Den Abeele, Ronald Schilderink, Felix Schneider, Raf Mols, Mans Minekus, Werner Weitschies, Joachim Brouwers, Jan Tack and Patrick Augustijns.
International Journal of Pharmaceutics 498, 2016
Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms.
Miriam Verwei, Mans Minekus, Evelijn Zeijdner, Ronald Schilderink, Robert Havenaar
International Journal of Pharmaceutics, 29 July 2013
In vitro gastrointestinal model (TIM) with predictive power, even for infants and children
TNO, The Netherlands, Erasmus MC - Sophia Children's Hospital, Dept. of Clinical Pharmacy and Dept. of Pediatric Surgery and Intensive Care
The AAPS Journal, Vol. 14, No. 2, June 2012
An Investigation into the Utility of a Multi-compartmental, Dynamic,System of the Upper Gastrointestinal Tract to Support Formulation Development and Establish Bioequivalence of Poorly Soluble Drugs, Paul A. Dickinson, et al,
Clinical Science, AstraZeneca R&D, Alderley Park, Macclesfield, UKSK10 4TG., Pharmaceutical Development, AstraZeneca R&D, Alderley Park, Macclesfield, UK.