(70af) Shape and size of polymorphic L-Glutamate crystals by batch cooling crystallisation

Batch cooling crystallisation is an important industrial unit operation often carried out in aqueous solutions. Measurement of crystal size and shape plays a major role in crystalliser control in order to improve product quality. Certain crystals grown from solution may exhibit polymorphism, which can significantly affect product properties such as bioavailability as well as impinging on downstream operations such as filtration and drying.

L-glutamate was considered as a model compound for this study as it crystallises from aqueous solution into two polymorphic forms, a and b, which are rhombic and acicular respectively. Full control of polymorph formation requires measurement of concentration of both of these different forms. In this study, cooling rate and initial solution concentration were chosen as manipulated variables to control polymorph formation. Rapid cooling with low solution concentration favours the formation of the a form while slow cooling with high concentration favours the b form. Crystal morphology interacts with other product quality measures, particularly crystal size. Currently, acquiring crystal size along with shape measurement is not readily achieved. Image analysis measures shape with size distribution but only for very small samples, and is not generally practical for control in the process industries. In this paper size distributions obtained by ultrasonic attenuation spectroscopy (UAS), laser diffraction spectroscopy (LDS), focused beam reflectance measurement (FBRM) and microscopic image analysis (MIA) are compared and the influence of crystal shape on size measurements is investigated.

Data obtained from UAS are combined with information on shape factor (circularity) from imaging to obtain true equivalent crystal size distribution (CSD). Data obtained from LDS are converted with a shape factor (sphericity) from imaging to obtain true CSD. In this paper, the influence of shape on size measurement is observed for these L-glutamate crystals.

Keywords: Crystal size distribution, Crystal shape, Ultrasonic attenuation, Laser diffraction, Image analysis, Focused beam reflectance measurement, cooling crystallisation

Li., M., D. Wilkinson, et al. (2005). "Comparison of particle size distributions measured using different techniques." Particulate Science and Technology 23: 1-20.