Ultrasonic attenuation spectroscopy was successfully applied for in-situ determination of particle size during the crystallization of a molecular crystal in two different polymorphic forms. The crystallization of L-glutamic acid was carried out under different cooling conditions by which the R-or -polymorphic form of L-glutamic was obtained preferentially. It is shown that each polymorph yields a characteristic acoustic attenuation due to the different habits of the two polymorphs. While it was found that ultrasonic attenuation measurements were less sensitive than turbidometric measurements for the determination of the onset of crystallization, ultrasonic attenuation measurements proved to be well behaved and provided particle sizing data for the prismatic crystals of the R-form of L-glutamic acid and an estimation of the primary dimensions of the -form needles. Growth rate and supersaturation data were derived from particle size and solid concentration results and correlated.

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.

In situ ultrasonic attenuation spectroscopy is used to examine the batch crystallization of urea from supersaturated aqueous and methanolic solutions. Benchmarking studies carried out on three cases are presented: noncrystallizing milled urea crystals in sunflower oil suspension, crystallizing pure urea from aqueous solution, and crystallizing urea in the presence of biuret habit modifier from methanol solution. In all cases, the technique was found to be capable of monitoring the size and concentration of anisotropic urea particles and it was responsive to the length and width of the needle-shaped crystals up to its upper size limit of 1000 µm. From measurements of changing particle size and concentration during crystallization, mass and linear crystal growth rates were calculated.