Why is neutral pH in the mouth favorable for absorbing weak bases?

• A. Neutral pH deactivates the drug
• B. Weak bases are more un-ionized at neutral pH, enhancing absorption
• C. Weak bases are ionized at neutral pH, enhancing absorption
• D. Neutral pH causes gastric emptying to slow

Answer: (B)

Absorption through the mouth relies on the drug crossing the lipid membranes of the mucosa, which is much easier for the unionized form than for a charged ion. A weak base exists in balance between its uncharged form (B) and its protonated, charged form (BH+). The relative amounts are governed by pH and the drug’s pKa. At near-neutral pH, the ratio shifts toward the uncharged B form for bases with typical pKa values in the physiological range, so more drug molecules are in a membrane-permeable state. That increased fraction of unionized base can diffuse across the mucosal barrier more effectively, leading to better absorption. If the environment were acidic, most of the drug would be protonated to BH+, which is charged and diffuses poorly, reducing absorption.