Limiting Solubilities and lonization Constants of Sparingly Soluble Compounds: Determination from Aqueous Potentiometric Titration Data Only

A new method is described for the concomitant determination of limiting solubilities and ionization constants of sparingly soluble compounds, i.e., drugs. Aqueous potentiometric titration data were recorded both before and after precipitation of the compound and subjected to computer-assisted analysis. Limiting solubilities and ionization constants were obtained for nucleoside transport inhibitors, viz., dilazep, soluflazine, and hexobendine. The method was validated by comparison of titration results for known antidepressants with data from the literature. The procedure was found to be rapid and reliable for compounds with limiting solubilities as low as 30 µM, and it circumvents problems of direct methods for measuring limiting solubilities.