Henderson-hasselbalch equation is inadequate for the measurement of transmembrane diffusion of drugs and buccal drug absorption is a useful alternative

1.1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly assessed from their degree of ionization or ratio unionized/ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch equation (HHEq).2.2. Buccal drug absorption (BA) at pH 5–9 has been proposed as an in vivo model for passage of drugs across lipid membranes.3.3. Area under the curve (AUC) of BA against pH 5–9 of 18 basic drugs has been reported to be significantly related to their pH dependent renal excretion.4.4. We have calculated, using HHEq, ratios U/I of 10 weak bases at pH 5–9 and 10 weak acids at pH 4–8, whose percentage BA at these pH levels was available in the literature.5.5. These ratios were not related to their %BA at corresponding pH levels.6.6. Therefore it is proposed that HHEq is inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA of drugs at pH 4–9 is a useful alternative.