277745 Development of an Empirical Framework for Monitoring CSD Using FBRM in Batch Crystallization

Tuesday, October 30, 2012: 1:20 PM
Crawford West (Westin )
Huayu Li, Martha Grover, Yoshiaki Kawajiri and Ronald W. Rousseau, School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA

Focus Beam Reflectance Measurement (FBRM) allows in-situ monitoring of crystallization processes. In order to utilize FBRM for control of crystallizers, accurate and robust measurement of crystal size distribution must be realized. To fulfill this goal, models for crystallization kinetics and the sensor are needed; the former is a population balance equation, while the latter converts the measured chord-length distribution (CLD) to the crystal size distribution (CSD) [1-3]. In our previous study, we proposed an empirical model for suspensions of paracetamol crystals in a non-solvent toluene [4]. The CLD obtained for a population of crystals of a specific size is referred to as a fingerprint. By obtaining fingerprints for different crystal sizes in toluene, the model was validated by investigating the linearity and additivity of fingerprint vectors.

In the present work, we apply the empirical model to a crystallization process. As paracetamol crystals of a certain size range are added into the saturated solution, the increase in total counts and changes in the chord-length histogram are recorded and analyzed to build the empirical model. We use a microscope and ATR-FTIR to confirm there is no significant transformation of crystal shape and no dissolution. Our investigations include the following: (1) a regime where the linearity of number of crystals and chord counts holds is identified, (2) linear additivity among different sizes of crystals is verified, (3) detectability of different crystal sizes by the FBRM is investigated, and (4) the most appropriate inversion technique is identified.

With the crystal size distribution estimated by the empirical model, liquid concentration and temperature recording, the full scope of the crystallization process is obtained for simulation purposes, such as parameter estimation and control scheme development. Such a framework is directly generated from practical FBRM data and requires no complicated physical modeling. Therefore, the small-scaled model can be applied in real-time conveniently to monitor and control crystallization processes.


  1. Yu, Z.Q., P.S. Chow, and R.B.H. Tan, "Interpretation of focused beam reflectance measurement (FBRM) data via simulated crystallization," Organic Process Research & Development, 2008. 12(4): p. 646-654.
  2. Ruf, A., J. Worlitschek, and M. Mazzotti, "Modeling and experimental analysis of PSD measurements through FBRM," Particle & Particle Systems Characterization, 2000. 17(4): p. 167-179.
  3. Kail, N., W. Marquardt, and H. Briesen, "Estimation of particle size distributions from focused beam reflectance measurements based on an optical model," Chemical Engineering Science, 2009. 64(5): p. 984-1000.
  4. Li, H., Y. Kawajiri, M. Grover, and R. W. Rousseau, "Estimation of Crystal Size Distribution with an empirical model of FBRM," AIChE Annual Meeting, Minneapolis, MN, October 2011

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