Concomitant Polymorphism of o-Aminobenzoic Acid in Antisolvent Crystallization

Concomitant polymorphism is the result of an interplay between thermodynamics and kinetics. By understanding this interplay and the effect of operational factors on it, concomitant polymorphism can be avoided, and product quality can be improved. Antisolvent crystallization of o-aminobenzoic acid (o-ABA) was performed in batch experiments at 298 K by rapidly mixing an ethanol solution of o-ABA with water as antisolvent. At low initial supersaturations the stable form I crystallizes, while at high initial supersaturations the metastable form II crystallizes. At intermediate initial supersaturations, concomitant polymorphism occurs. It was observed that at higher supersaturations, form II has a higher growth rate than does form I, while the reverse occurs at lower supersaturations. At intermediate supersaturations, the growth rates of both forms are similar, and a nucleation assessment indicates that nucleation rates are similar as well. It was therefore concluded that not the solvent-mediated transformation but rather concomitant crystallization is responsible for the observed concomitant polymorphs. When all supersaturation toward form II is depleted, the solvent-mediated transformation starts. The solvent-mediated transformation of form II to form I is quite rapid, even at high water fraction. Pure form I is readily obtained by allowing sufficient time for the polymorph transformation to finish.