Attenuated total reflectance Fourier transform infrared (ATR–FTIR) spectroscopy and focused-beam reflectance measurement (FBRM) instruments are commonly used for monitoring, model development, and feedback control of crystallization processes (Simon et al., 2015). ATR–FTIR is typically used to monitor the solution composition and—in conjunction with temperature measurements—the supersaturation, while FBRM provides an estimate of the number of crystals suspended in solution via the chord count.
In this work we use ATR–FTIR to monitor the solution supersaturation—as is typically done—but also use ATR-FTIR to infer the total crystal mass via a mass balance. This provides a second measured crystal property (in addition to the chord count provided by FBRM) and suggests a new way to view crystallization: as a trajectory in the phase space mapped out by the crystal mass and chord count. This yields a new framework that facilitates an intuitive understanding of the crystallization kinetics and promotes the development of model-free schemes that directly control the measured crystal properties.
In this talk, we will discuss how we synthesize dynamic measurement data from ATR-FTIR and FBRM to cast crystallization as a trajectory in the 2D mass-count space, and show how this perspective reveals a new framework for monitoring and controlling crystallization. In addition, we will show how the framework can be applied to: 1) elucidate crystallization kinetics; 2) interpret the methods by which supersaturation control (SSC) (Fujiwara et al., 2002) and direct nucleation control (DNC) (Abu Bakar et al., 2009) produce large crystals; and 3) develop new feedback control schemes that can be applied to produce crystals of pre-selected average size. Batch cooling crystallization of sodium nitrate and sodium sulfate in an aqueous solution will be shown as a case study.
Abu Bakar, M. R., Nagy, Z. K., Saleemi, A. N. and Rielly, C. D. 2009. The Impact of Direct Nucleation Control on Crystal Size Distribution in Pharmaceutical Crystallization Processes. Crystal Growth & Design 9
Fujiwara, M., Chow, P. S., Ma, D. L. and Braatz, R. D. 2002. Paracetamol Crystallization Using Laser Backscattering and ATR-FTIR Spectroscopy: Metastability, Agglomeration, and Control. Crystal Growth & Design 2, 363-370
Simon, L. L., Pataki, H., Marosi, G., Meemken, F., Hungerbühler, K., Baiker, A., Tummala, S., Glennon, B., Kuentz, M., Steele, G., Kramer, H. J. M., Rydzak, J. W., Chen, Z., Morris, J., Kjell, F., Singh, R., Gani, R., Gernaey, K. V., Louhi-Kultanen, M., O’Reilly, J., Sandler, N., Antikainen, O., Yliruusi, J., Frohberg, P., Ulrich, J., Braatz, R. D., Leyssens, T., Von Stosch, M., Oliveira, R., Tan, R. B. H., Wu, H., Khan, M., O’Grady, D., Pandey, A., Westra, R., Delle-Case, E., Pape, D., Angelosante, D., Maret, Y., Steiger, O., Lenner, M., Abbou-Oucherif, K., Nagy, Z. K., Litster, J. D., Kamaraju, V. K. and Chiu, M.-S. 2015. Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review. Organic Process Research \& Development