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

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 degrees 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.

Automated summary

The study showed that using ultrasound combined with seed guidance effectively increased the yield and purity of form-I of o-aminobenzoic acid. Compared to silent conditions in flow crystallization experiments, ultrasound improved seed dispersion and reduced wall nucleation, resulting in higher quality pure product.