Solubility of organic hydrochlorides

Abstract

The solubilities of two polysubstituted 1,3‐dioxolanes, each containing a 4‐(2′‐piperidyl) substituent, were examined as a function of pH, temperature, and solvent composition. Mathematical equations describing the total solubility at any arbitrary pH in terms of the independent solubilities of the hydrochloride and free base species and the dissociation constant of the salt were derived and fitted to the data with good result. Alternatively, a method of estimating the true pK 'a of a hydrochloride from the solubility profile at a given temperature is indicated. The data show that the shape of the pH profile is more dependent on the solubility of the free base than on that of the hydrochloride. The free base solubility determines the pH range in which the solubility abruptly drops from that of the soluble salt to that of the relatively insoluble free amine. To shift the pH‐solubility profile to higher pH values, as may be required in formulation, it is necessary to increase the solubility of the free base. Methods and solvents are indicated whereby this can be accomplished without appreciably affecting the solubility of the hydrochloride form. Copyright © 1972 Wiley‐Liss, Inc., A Wiley Company