Physiology questions

We developed, and are now optimizing and validating, the TIMpsf (patent pending). This is a separate unit, whether or not connected to the TIM system, for accurate and controlled simulation of the gastro-intestinal pressure and shear forces.

The transit time in duodenum is approx. 10-15 min. Transit time in jejunum and ileum is approx. 3.5 h for both fasting and fed state. The ileal emptying is controlled via a computer ‘protocol’ based on an equation calculated from in vivo data.

The initial pH in the duodenum is 6.5. Controlled by the secretion of bicarbonate the pH for the fasting state is fixed at pH 6.3 and for the fed state the pH decreases in 2-3 h to pH 5.9. The set-points for the pH in jejunum and ileum compartments are 6.5 and 7.4, resp.

There are semi-permeable membrane cartridges connected to the intestine compartments of the TIM systems. The membranes are not intended to simulate  (passive/active) mucosal transport, such as intestinal cell lines and intestinal segments. Instead, the membranes are dialysis/filtration membranes that enable us to remove, from the intestinal lumen, the (low MW) compounds that are released from the (food) matrix or drug dosage form, solubilized, and available for intestinal absorption. This is called the ‘bioaccessible fraction’ (or pharmaceutical available fraction). TIM systems can accurately predict what fractions are bioaccessible, thus available for mucosal transport and absorption.

Yes, this can be done by selecting a higher pH set-point curve. This will result in less acid secretion. In this way we can simulate inter-individual variations or effects of other drugs.