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PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

➢ It is important therefore for poorly soluble weak bases to dissolve rapidly in

the stomach, as the rate of dissolution in the small intestine will be much slower.

Example:

➢ The antifungal drug ketoconazole, a weak base, is particularly sensitive to

gastric pH.

➢ Dosing ketoconazole 2 hours after the administration of the H2 blocker

cimetidine, which reduces gastric acid secretion, results in a significantly

reduced rate and extent of absorption.

(d) Salt formation

▪ The dissolution rate of a weakly acidic drug in gastric fluid (pH 1-3.5) will be relatively

low.

If the pH in the diffusion layer could be
increased,

then the solubility, Cs, and hence the
dissolution rate, would be increased

▪ The pH of the diffusion layer would be increased if the chemical nature of the

weakly acidic drug were changed from that of the free acid to a basic salt, for

example the sodium or potassium form of the free acid.

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