Molecular, Crystal, and Surface Chemistry of p‑Aminobenzoic Acid and the Interrelationship between Its Solution-Phase Crystallization and Solid-Form Selectivity: A Review

An overview of some selective research into the solution-phase crystallization and polymorphic behavior of the organic compound, p-aminobenzoic acid (PABA), a representative model compound for a small-molecule pharmaceutical, is presented. The review highlights and interlinks the crystal science underpinning its molecular properties, crystallographic structures, intermolecular crystal chemistry, solution structuring properties, crystallizability, nucleation and growth kinetics and mechanisms, polymorph selection and solvent-mediated morphology, and surface chemistry using both computational modeling and experimental studies. The review mostly focuses on studies of the formation of the α-polymorphic form and how solvent selection and additive action can mediate the crystallization and polymorphic direction process. Additionally, an overview is provided into the crystallographic structures of the four polymorphic forms of PABA and their similarities in terms of both their molecular structure and intermolecular packing. The potential for transferring the fundamental understanding of PABA crystallization to address larger-scale crystallization processes and their control through integrating crystal morphology control is also highlighted.