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To have 30% of this compound in its unionised form when the bulk pH is 7, would require a surface pH of about 3.4, which is lower than anticipated. Again, however, we must remember that absorption and ionisation processes are dynamic processes. As the unionised species is absorbed, so the level of [U] in the bulk falls and, because of a shift in equilibrium, more of the unionised species appears in the bulk. In fact, if a pH of 5.3 is taken as the pH of the absorbing surface, the results in Table 9.2 become more explicable, as we discuss in the next section.

9.1.3 Problems in the quantitative application of the pH-partition hypothesis

There are several reasons why the pH-partition hypothesis cannot be applied quantitatively in practical situations. Some are discussed here.

Variability in pH conditions

The variation in the stomach pH in human subjects is remarkable, bearing in mind that each pH unit represents a ten-fold difference in hydrogen ion concentration. While the normally quoted range of stomach pH is 1-3, studies using pH-sensitive radiotelemetric capsules have shown a greater spread of values, ranging up to pH 7 as seen in Fig. 10.2 in Chapter 10. This means that the dissolution rate of many drugs will vary markedly in individuals - this is indeed one of the reasons for individual-to-individual variation in drug availability.

The scope for variation in the small intestine is less, although in some pathological states the pH of the duodenum may be quite low owing to hypersecretion of acid in the stomach. Table 9.3 lists the normal pH of

Table 9.3 pH of blood and contents of the human

alimentary tracta

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