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Tiny TIM

TinyTIM (Fig. 5.3) is a simplified version of the TIM-1, designed to increase the throughput as compared to TIM-1, with focus on studies that do not need separate intestinal steps. The TinyTIM is used with the same gastric compartment as TIM-1

Fig. 5.2 Gastric emptying (circles, t1/2 = 80 min, β = 2) and ileal emptying curve (squares, t1/2 = 220 min, β = 2.2) to control transit of a solid meal in TIM-1

Table 5.1 Typical parameter settings for digestion of a high fat meal in TIM-1 with filters

Volume (ml)

Stomach: 300, duodenum: 55, jejunum: 130, ileum: 130

Meal size (g)

300

Gastric secretion (ml/min)

1

Gastric emptying curve

t1/2 = 80 min, β = 2

Gastric pH curve (time, pH)

(0, 5.2) (30, 3.2) (60, 2.2) (120, 1.7)

Bile secretion (ml/min)

0.5

Pancreatin/electrolytes (ml/min)

0.5

Ileal emptying curve

t1/2 = 220 min, β = 2.2

Small intestinal pH

Duodenum: 6.2, jejunum: 6.5, ileum: 7.4

Filtration rate (ml/min)

Jejunum: 4.5, ileum: 4.5

Fig. 5.3 Schematic presentation of TinyTIM, equipped with a dialysis membrane to study the bioaccessibility of water soluble compounds. A. gastric compartment; B. pyloric sphincter; C. duodenal compartment; D. gastric secretion; E. duodenal secretion; F. pre-filter; G. pH electrodes; H. dialysis membrane; I. dialysis system; J. pressure sensor; K. level sensor

when the ratio between amount of food and ingested material, such as pharmaceutical formulations, is important. For other experiments, a half size gastric compartment is used. All functions of the gastric compartment are similar to the gastric compartment of TIM-1. TinyTIM has a single small intestinal compartment instead of three and no ileal efflux. All fluids entering the small intestinal compartment are removed through the filtrationor dialysis-membrane. This implies that small intestinal transit is simulated by assuming a plug of chyme traveling through the small intestine, instead of a “flow through” compartment such as in TIM-1.

Advanced Gastric Compartment (TIM-agc)

In the standard gastric compartment, the meal is mixed to obtain a homogenized gastric content and a consequent predictable gastric emptying of compounds. This is particularly important to compare the digestion of compounds under exactly controlled conditions. In order to include the effect of gastric motility on the gastric behavior of food components and pharmaceuticals, a gastric compartment is designed that mimics the shape and motility of the stomach in a more realistic manner (Fig. 5.4). The system consists of a body part with a flexible wall that gradually contracts to simulate gastric tone and consequent reduction of gastric volume during emptying. Two antral units can be moved to simulate mixing by an antral wave. A valve is synchronized with an antral wave to simulate the opening of the pyloric sphincter during gastric emptying. Similar to other TIM models, the contractions are achieved by modulating the pressure on water that is circulated in the space between a glass jacket and a flexible membrane. All contractile movements and the resulting mixing and pressure profiles are accurately controlled and synchronized. Motility patterns as well as gastric emptying and secretion of digestive fluids are dictated by a predetermined protocol that describes a specific condition (e.g. fed or fasting) in time. A study has been performed in both the TIM-agc and human volunteers to compare gastric pressure profiles, using a smartpill® (Given Imaging GmbH, Hamburg, Germany) (Fig. 5.5, Minekus et al. 2013).

Fig. 5.4 Schematic presentation of the TIM advanced gastric compartment (TIM-agc). The left and right pictures show a filled and completely empty gastric compartment, respectively. A. body; B. proximal antrum; C. distal antrum; D. pyloric sphincter

Fig. 5.5 Gastric pressure profile measured with a smartpill® in the TIM-agc (left) as compared to an in vivo gastric pressure profile measured with a smartpill® during the digestive phase

 
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