Often neglected steps in transforming drug solubility from single measurement in pure water to physiologically-appropriate solubility-pH.

ABSTRACT:

Background and purpose

The solubility of weakly-ionizable drugs in pure water, S_w, is commonly measured. The pH-dependent properties of the saturated solutions can be surprisingly complex in subtle ways. This commentary examines the characteristics of such measurements through case studies of 32 free acids, bases, and ampholytes (including crocetin, glibenclamide, mellitic acid, quercetin, bedaquiline, brigatinib, imatinib, celecoxib, and lysine), using published water solubility data.

Computational approach

Usually, in such saturated solutions, the ionic strength, I _w, is close to zero. When the pH is adjusted away from pH_w, the ionic strength increases, substantially in some cases (e.g. I _w > 10 M at pH 7.4 for mell

SUBMITTER: Avdeef A 

PROVIDER: S-EPMC11954141 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature