Closed‐Loop Control of Reactive Crystallization PART II: Polymorphism Control ofL‐Glutamic Acid by Sonocrystallization and Seeding

Abstract The impact of different nucleation methods with controlled supersaturation on the polymorphism ofL‐glutamic acid crystals was studied in a 50 dm3semi‐batch crystallizer, in which 1.5 M H2SO4was fed into a 1.5 M monosodium glutamate solution. Supersaturation was controlled by a feedback loop based on measured ATR‐FTIR spectra and on a thermodynamic model developed in house. Ultrasound‐initiated nucleation produced pure α‐polymorph (over 99.5 wt %) in the end product crystals at 1 mol/dm3supersaturation. Seeded crystallization also produced almost pure α‐polymorph crystals (over 93 wt %), whereas spontaneous nucleation produced a polymorph mixture (from 30–70 wt %) under the same operating conditions. This indicates that supersaturation‐controlled sonocrystallization can be used to control polymorphism in crystals. The novelty herein is the simplicity of the method directing the generation of a desired polymorph.