TNO (gastro-) Intestinal Models (“TIM”) are model systems mimicking the digestive tract. The models are dynamic computer controlled multi-compartmental systems with adjustable parameters for the physiological conditions of the stomach and intestine. Temperature, peristalsis, bile secretion, secretion of saliva, stomach and pancreas enzymes are all fully adjustable. The TIM systems are being used to study the behavior of oral products during transit through the stomach, the small intestine and large intestine. Commonly performed studies concern the digestibility of food and food components, the bioaccessibility for absorption of pharmaceutical compounds, proteins, fat, minerals and (water- and fat-soluble) vitamins. [1] [2] [3] [4] [5] [6] [7]

There are different models for the stomach and small intestine (TIM-1 and Tiny-TIM) and a model simulating the physiological conditions of the colon (TIM-2).

The TIM-1 system consists of a stomach compartment and 3 compartments for the small intestine, the duodenum, jejunum and ileum. The Tiny-TIM system consists of a stomach compartment and one single compartment for the small intestine. Samples can be harvested for analysis from these models from any compartment at any time.

TIM-2 simulates the colon, containing the microbiota as found in human colon. This model serves as a tool to study fermentation of non-digestible food components (fibers and prebiotics) and the release of drugs specifically targeted for the colon.[8]


References

  1. ↑ Barker, R., Abrahamsson, B., Kruusmägi, M. (2014). "Application and validation of an advanced gastro-intestinal in vitro model for evaluation of drug product performance in pharmaceutical development." J. Pharm. Sci., 103 (11). DOI 10.1002/jps.24177.
  2. ↑ David, S.E., Strozyk, M.M. & Naylor, T.A. (2010). "Using TNO gastro-Intestinal Model (TIM-1) to screen potential formulations for a poorly soluble development compound." J. Pharm. Pharmacol., 62: p1236-1237.
  3. ↑ Dickinson, P.A., Abu Rmaileh, R., Ashworth, L., Barker, R.A., Burke, W.M., Patterson, C.M., Stainforth, N. and Yasin, M. (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." AAPS Journal, 14 (2): p196-205.
  4. ↑ Havenaar, R., Anneveld, B., Hanff, L.M., de Wildt, S.N., de Koning, B.A.E., Mooij, M.G., Lelieveld, J.P.A., Minekus, M. (2013). "In vitro gastrointestinal model (TIM) with predictive power, even for infants and children?" Internat. J. Pharm., 457: p327-332.
  5. ↑ Mitea, C., Havenaar, R., Drijfhout, J.W., Edens, L., Dekking, L. and Koning, F. (2008). "Efficient degradation of gluten by prolyl endoprotease in gastrointestinal model: Implications for coeliac disease." Gut 57: p25-32.
  6. ↑ Smeets-Peeters, M.J.E., Minekus, M., Havenaar, R., Schaafsma, G., Verstegen, M.W.A. (1999). "Description of a dynamic in vitro model of the dog gastrointestinal tract and an evaluation of various transit times for protein and calcium." ATLA 27: p935-949.
  7. ↑ Helbig, A., Silletti, E., van Aken, G.A., Oosterveld, A., Minekus, M., Hamer, R.J., Gruppen, H. (2013). "Lipid digestion of protein stabilized emulsions investigated in a dynamic in vitro gastro-intestinal model system." Food Dig. 4: p58–68. DOI 10.1007/s13228-012-0029-6.
  8. ↑ Minekus, M., Smeets-Peeters, M.J.E., Bernalier, A., Marol-Bonnin, S., Havenaar, R., Marteau, P., Alric, M., Fonty, G., and Huis in ‘t Veld, J.H.J. (1999). "A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products." Appl. Microb. Biotechn. 53: p108-114.


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