Characterization of particle size and its distribution during the crystallization of organic fine chemical products as measured in situ using ultrasonic attenuation spectroscopy

The potential application of ultrasonic attenuation spectroscopy to the in situ examination of solution phase crystallization processes is examined through studies carried out on two organic compounds: urea and (L)-glutamic acid. For this study a commercial ultrasonic spectrometer [Ultrasizer by Malvern Instruments Ltd., F. Alba, U.S. Patent 5,121,629 (1992)] was used. A particle size analysis was carried out in an attempt to monitor the crystal size distributions of the crystals growing within the mother liquor. While this technique was found to be of limited effectiveness for the monitoring of the crystallization of urea, due to the formation of high aspect ratio needle crystals, whose long axial size is beyond the range of the technique (0.01 μm–1000 μm), good results were obtained with prismatic (L)-glutamic acid crystals. The size evolution of the latter during crystal growth was successfully monitored throughout the crystallization process.