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Anion concentration (10~2 mol kg-1)

Figure 9.8 Apparent partition coefficients for chlorpromazine between n-octanol and aqueous buffers at pH 3.9, in the presence of various anions at 30°C: O, chloride; •, propanesulfonate; <s, ethanesulfonate; A, methanesulfonate.

Reproduced from L. S. Murthy and G. Zografi, J. Pharm. Sci., 59, 1281 (1970).

Anion concentration (10~2 mol kg-1)

Figure 9.8 Apparent partition coefficients for chlorpromazine between n-octanol and aqueous buffers at pH 3.9, in the presence of various anions at 30°C: O, chloride; •, propanesulfonate; <s, ethanesulfonate; A, methanesulfonate.

Reproduced from L. S. Murthy and G. Zografi, J. Pharm. Sci., 59, 1281 (1970).

9.2 The oral route and oral absorption

9.2.1 Drug absorption from the gastrointestinal tract

The oral route is the most popular and convenient route of drug administration for those drugs which can survive the acid of the stomach, which are resistant to enzymatic attack, and which are absorbed across gastrointestinal membranes. The functions of the gastrointestinal tract are the digestion and absorption of foods and other nutrients and it is not easy to separate these two functions from that of drug delivery. Indeed, the natural processes in the gut frequently influence the absorption of drugs. This is not surprising when it is considered that approximately 500 g of solid and up to 2.5 litres of fluid are ingested on average each day. As well as this oral intake, an estimated 30 litres of endogenous fluid are excreted each day into the intestine.

The pH of the gut contents and the presence of enzymes, foodstuffs, bile salts, fat and the microbial flora will all influence drug absorption. The complexity of the absorbing surfaces means that a simple physicochemical approach to drug absorption remains an approach to the problem and not the complete picture, as described above. Whatever the limitations of theory - and one should not expect simple theories to hold in the complex and dynamic circumstances which are involved in drug absorption - theory provides a starting point in rationalising the behaviour of drugs in the gastrointestinal tract. While most drugs are absorbed by passive diffusion across the lipid membranes separating the gut contents from the rest of the body, certain molecules that resemble naturally occurring substances are actively transported by special mechanisms.

We first consider the physiological situation which might impinge on passive drug absorption. The delivery of macromolecules, including peptides and proteins, is treated in a separate chapter.

Particulate absorption from the gut

While the general rule is that only drugs in

1200 cm3 water 1500 cm3 saliva

500 cm3 bile

1500 cm3 pancreatic secretion Duodenum

Large Intestine

Small Intestine

Appendix

1200 cm3 water 1500 cm3 saliva

500 cm3 bile

Large Intestine

Small Intestine

Appendix

1500 cm gastric secretion

Pancreas

Anal canal

Rectum 350 cm3

1500 cm gastric secretion

Pancreas

1500 cm3 intestinal secretion

8500 cm3

Anal canal

Rectum 350 cm3

Cholesterol

Bile salts

Portal

Food

Antacids

VpH1-3 Volume ? Residence time ?

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