Influence of ultrasound on the nucleation of polymorphs of p-aminobenzoic acid

p-Aminobenzoic acid crystallizes in two different polymorphic forms: the alpha-form and the beta-form. The alpha-form crystals are needle-shaped, while the beta-form crystals have a more favorable prismatic shape. The system is enantiotropic with the transition temperature at approximately 25 degrees C. Below the transition temperature, the beta-form is the thermodynamically stable polymorph but can only be produced at very slow supersaturation generation either in water or in ethyl acetate. In the present work, the influence of ultrasound on the nucleation of p-aminobenzoic acid polymorphs has been investigated by use of several different sonication intensities and schemes. It is shown that sonication significantly reduces the induction time for nucleation. By using controlled sonication, we were able to more reproducibly crystallize the beta-form at more reasonable cooling rates. In addition, sonication is found to quite selectively favor the appearance of the beta-polymorph. It is even possible to produce the pure beta-form above the transition temperature where it is the metastable form and impossible to produce without sonication. The alpha-form structure is based on centro symmetric dimers formed by the association of carboxylic acid groups, while the beta-form contains four-membered hydrogen-bonded rings of alternating amino and carboxylic acid groups. It is suggested that ultrasound disturbs the building up of the dimers in the solution and thus favors the crystallization of the beta-polymorph.