Journal
CHEMICAL ENGINEERING RESEARCH & DESIGN
Volume 88, Issue 8A, Pages 1108-1119Publisher
ELSEVIER
DOI: 10.1016/j.cherd.2010.02.010
Keywords
Supersaturation; Crystallization; ATR-FTIR; FBRM; Feedback control; Scale-up
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Funding
- Science Foundation Ireland [07/SRC/B1158]
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Supersaturation is the key driving force in crystallization operations, determining nucleation and growth kinetics, and heavily influencing physical mechanisms such as agglomeration. Therefore, knowledge of the bulk supersaturation during crystallization can greatly enhance process understanding and optimization. In this paper, a method which facilitates the calibration-free use of in situ ATR-FTIR for crystallization development and control is presented. This methodology uses solute-specific ATR-FTIR absorption peak heights to describe solute solubility and dissolved concentration and, in turn, supersaturation, for the optimization of cooling crystallizations of an active pharmaceutical ingredient (API) and benzoic acid. The approach presented facilitates rapid process understanding, design and optimization. Specifically, the potential to significantly reduce cycle time for both systems studies is demonstrated. In addition, the potential of the method to form the basis of a process control strategy for batch crystallization is successfully demonstrated. (C) 2010 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
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