Figure 2.4 Schematic of the villi ''fingers'' covered by a monolayer of epithelial cells, separating the lumen from the blood capillary network [63,69]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]

stomach releases its contents periodically, and the rate depends on the contents. On an empty stomach, 200 mL of water have a transit half-life of 0.1-0.4 h, but solids (such as tablets) may reside for 0.5-3 h, with larger particles held back the longest. Food is retained for 0.5-13 h; fatty food and large particles are held the longest time. Transit time through the jejunum and ileum is about 3-5 h. Digesting food may stay in the colon for 7-20 h, depending on the sleep phase. Fatty foods trigger the release of bile acids, phospholipids, and biliary proteins via the hepatic/bile ducts into the duodenum. Bile acids and lecithin combine to form mixed micelles, which help solubilize lipid molecules, such as cholesterol (or highly lipophilic drugs). Under fasted conditions, the bile : lecithin concentrations in the small intestine are approximately 4 : 1 mM, but a fatty meal can raise the level to about 15 : 4 mM [68,71]. Thus, maximal absorption of drug products takes place in the jejunum and ileum over a period of 3-5 h, in a pH range of 4.5-8.0. This suggests that weak acids ought to be better absorbed in the jejunum, and weak bases in the ileum.

The surface area in the luminal side of the small intestine per unit length of the serosal (blood) side is enormous in the proximal jejunum, and steadily decreases (to about 20% of the starting value [62]) in the distal portions of the small intestine. The surface area is increased threefold [69] by ridges oriented circumferentially around the lumen. Similar folds are found in all segments of the GIT, except the mouth and esophagus [66]. Further 4-10-fold expansion [62,69] of the surface is produced by the villi structures, shown schematically in Fig. 2.4. The layer of epithelial cells lining the villi structures separate the lumen from the circulatory system. Epithelial cells are made in the crypt folds of the villi, and take about

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