Near infrared spectroscopy (NIR) uses fiber‐optics for rapid data transmission, is robust, simple, and sensitive at both low and high solution concentrations. Therefore, it is particularly suitable for monitoring industrial processes. This study investigates the use of NIR for monitoring batch cooling crystallization processes, and emphasis is placed on applying genetic algorithm (GA) for wavelength selection in partial least squares calibration model development. The calibration data was collected for under‐saturated and saturated solutions, as well as for α‐ and β‐form crystal slurries of L‐glutamic acid at a variety of solution concentrations, temperatures, and solid concentrations and sizes. The GA method proves to be capable of effectively selecting a small number of wavelengths and the models thus developed give improved prediction performance in terms of generalization capability compared to models derived using the full spectrum. The developed models are successfully applied to monitoring batch cooling crystallization of L‐glutamic acid under seeded and unseeded conditions and with varied cooling rates.

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Despite being widely used in agriculture, food production and environmental monitoring and regarded as online chromatograph in petrochemical and biochemical industries, near infrared spectroscopy (NIR) has found difficulties in its application to processes of particle formation through crystallization or precipitation where solids suspended in solutions cause problems in instrumentation as well as distortion of the spectra. The research work reported here was motivated by the speculative idea that the effect of particles on the NIR spectra in effect brings an opportunity instead: the spectra might contain useful information of both the solid and liquid phases. Through carefully designed experiments using both glutamic acid solutions and slurries of varied solid concentrations and particle size and temperature ranges and with the help of chemometric data analysis, it was found that the NIR spectra clearly contain sensitive information about the size, solid concentration, liquid concentration as well as polymorphs of crystals, providing the possibility of using the instrument for simultaneous measurement of the multiple properties of both phases.

Psilocybin, a serotonergic agonist, was granted a "breakthrough therapy" status by the Food and Drug Administration for clinical trials involving major depressive disorder and treatment-resistant depression. The direct phosphorylation of psilocin to psilocybin that uses a fast crystallization associated with a kinetically controlled process resulted in a smaller particle size distribution. Herein, the measurement of the metastable zone width (MSZW) and nucleation induction enabled a thermodynamically controlled crystallization process, which leads to the formation of a crystal structure with stronger interactions, controlled particle size distribution (PSD), and improved impurity profile. Employing a high-resolution inline microscopy viewer allowed the realtime monitoring of the crystallization process and the measurement of the particle size. We also present a comprehensive study of the formation of polymorph B (trihydrate), polymorph A (anhydrate), and polymorph H (anhydrate) using water recrystallization, which indicates that the formation of polymorph B (trihydrate) is independent of the crystallization method. However, polymorphs A and H are dependent on the mode of drying: drying at room temperature under vacuum gives rise to mainly polymorph A, and when heated even at relatively low temperatures, a mixture of polymorphs A and H beings to form.