Crystallization of α and β Polymorphs of Para Aminobenzoic Acid from Mixed Solvents by Slow Evaporation Method

Abstract

Para aminobenzoic acid (p-ABA), a well-known pharmaceutical material with a challenging polymorphic nature, is chosen for study in this paper. The material has four reported polymorphs, containing two solution forms (α and β), a vapor form, and a high-pressure form. The solution-grown forms α and β are experimentally grown using mixed solvents of water and isopropyl alcohol with nine different mixing compositions at temperatures of 298, 303, and 308 K. The solubility of the commercially available p-ABA is calculated gravimetrically, and the polymorphic crystals are grown using the slow solvent evaporation method for all the mixing ratios at different temperatures. A ternary diagram constructed on the solubility of p-ABA in mixed solvents gives an insight into the nucleation nature of two polymorphs. To understand the nature of nucleation and growth of two forms of p-ABA, an in situ microscopic study is carried out, and the grown crystals are characterized using powder X-ray diffraction analysis and differential scanning calorimetry. This also confirmed that the grown crystals are two solutions grown polymorphs of para aminobenzoic acid, both belonging to monoclinic systems with P2₁/n space group.