Crystallization of a Salt of a Weak Organic Acid and Base: Solubility Relations, Supersaturation Control and Polymorphic Behavior

Control of crystallization processes for organic salts is of importance to the pharmaceutical industry as many
active pharmaceutical materials are marketed as salts. In this study, a method for estimating the solubility
product of a salt of a weak acid and weak base from measured pH-solubility data is described for the first
time. This allows calculation of the supersaturation of solutions at known pH. Ethylenediammonium 3,5-dinitrobenzoate is a polymorphic organic salt. A detailed study of the effects of pH, supersaturation, and
temperature of crystallization on the physical properties of this salt shows that the desired polymorph may be
produced by appropriate selection of the pH and supersaturation of crystallization. Crystal morphology is
also controlled by these crystallization conditions.