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 R- and -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 R-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. © 2009 American Chemical Society.

• Massachusetts Institute of Technology (MIT) (MIT)

• Control

1. ATR-FTIR
2. Control
3. crystallization
4. FBRM
5. metastable form
6. Research Article