Selective Crystallization of the Metastable α-Form of l-Glutamic Acid using Concentration Feedback Control

• Published in: Crystal growth & design 2009-07, Vol.9 (7), p.3044-3051
• Main Authors: Kee, Nicholas C. S, Tan, Reginald B. H, Braatz, Richard D
• Format: Article
• Language: English
• Subjects: Condensed matter: structure, mechanical and thermal properties; Crystalline state (including molecular motions in solids); Crystallographic aspects of phase transformations; pressure effects; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; Physics; Solid-solid transitions; Solubility, segregation, and mixing; phase separation; Specific phase transitions; Structure of solids and liquids; crystallography; Structure of specific crystalline solids
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg800546u

A systematic methodology is presented for the selective crystallization of the metastable form of a monotropic dimorph, l-glutamic acid, for batch cooling crystallization. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy coupled with chemometrics was used to determine the solute concentration and solubility curves of both α- and β-forms of l-glutamic acid in aqueous solution. The metastable limit associated with secondary nucleation for a seeded system was determined using laser backscattering (focused beam reflectance measurement, FBRM). Batch crystallizations seeded with the metastable α-form crystals following various preset supersaturation profiles were implemented using concentration feedback control which regulated the cooling rate based on the in situ measurement of solute concentration. Batch crystallizations operated at constant relative supersaturation in an appropriate temperature range prevented secondary nucleation of both polymorph types and were successful in selectively growing large metastable crystals with uniform size.