Which form is favored by a weak acid in the acidic environment of the stomach?

• A. Ionized
• B. Unionized
• C. Both
• D. Amphoteric

Answer: (B)

In acidic environments, a weak acid tends to stay in its protonated, unionized form. This follows from the Henderson–Hasselbalch relation pH = pKa + log([A-]/[HA]); rearranged, the ratio [A-]/[HA] = 10^(pH − pKa). When the pH is lower than the pKa (as in the stomach, which is very acidic), this ratio is less than 1, so the protonated form HA (unionized) dominates. The stomach’s low pH thus favors the unionized form of a weak acid. This unionized form is less polar and more lipid-soluble, which affects how the drug crosses gastric membranes. In contrast, in higher pH environments like the intestine, the pH exceeds the pKa and the ionized form A- becomes more prevalent.