Page 111 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

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

▪ The pH of the diffusion layer surrounding the salt form would be higher (e.g. 5-6) than

the low bulk pH (1-3.5) of the gastric fluids because of the neutralizing action of the

strong ions (Na+ or K+) present in the diffusion layer
.
▪ Because the salt form of the weakly acidic drug has a relatively high solubility at the

elevated pH in the diffusion layer, dissolution of the drug particles will take place at a
faster rate

▪ When dissolved drug diffuses out of the diffusion layer into the bulk of the gastric
fluid, where the pH is lower, precipitation of the free acid form is likely to occur.

o This will be a result of the overall solubility exhibited by the drug at the lower bulk

pH

o Thus, the free acid form of the drug in solution, which is in excess of its solubility at

the bulk pH of gastric fluid, will precipitate out, leaving a saturated (or near-saturated)

solution of free acid in gastric fluid.

o Often this precipitated free acid will be in the form of very fine, non-ionized wetted

particles which exhibit a very large total effective surface area in contact with gastric

fluids.

o This large total effective surface area will facilitate rapid re-dissolution of the

precipitated particles of free acid when additional gastric fluid becomes available.

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