Ultrasound as a tool for polymorph control and high yield in flow crystallization

Abstract

Ortho-aminobenzoic acid (o-ABA) has three polymorphs from which form-I is the most stable and forms-II and III are meta–stable ones at 25 °C. In flow crystallization, the meta-stable form-II is quite persistent and prevents nucleation of the stable form-I. This is contrary to batch crystallization and possibly a result of high local supersaturation. In this work, seeded, anti-solvent crystallization of o-ABA was conducted to overcome nucleation of the meta-stable form and obtain a high yield of form-I. Experiments were conducted in a tubular flow crystallizer under silent and sonicated conditions. Seeding was effective in producing pure form-I only when ultrasound was applied. Under silent conditions, poor dispersion of seeds and heterogeneous wall nucleation led to the growth of form - II. Ultrasound improved dispersion and reduced nucleation on walls and thus a pure form-I product was obtained. Particle sizes and SEM images showed evidence of secondary nucleation as the mechanism for form-I occurring in seeded, sonicated experiments rather than seed growth. A high yield, 48% by mass and 85% of maximum crystallizable mass, could be achieved. Ultrasound increased the potential of the flow crystallization system by combining high yield with polymorph control.