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 P2 1 /n space group.