期刊
AICHE JOURNAL
卷 55, 期 10, 页码 2631-2645出版社
WILEY
DOI: 10.1002/aic.11879
关键词
pharmaceutical crystallization; polymorphism; nonlinear model predictive control; extended predictive self-adaptive control; unscented Kalman filter
Polymorphism, a phenomenon where a substance can have more than one crystal forms, has recently become a major interest to the food, speciality chemical, and pharmaceutical industries. The different physical properties for polymorphs such as solubility, morphology, and dissolution rate may jeopardize operability or product quality, resulting in significant effort in controlling crystallization processes to ensure consistent production of the desired polymorph. Here, a nonlinear model predictive control (NMPC) strategy is developed for the polymorphic transformation Of L-glutamic acid from the metastable alpha-form to the stable beta-form crystals. The robustness of the proposed NMPC strategy to parameter perturbations is compared with temperature control (T-control), concentration control (C-control), and quadratic matrix control with successive linearization (SL-QDMC). Simulation studies show that T-control is the least robust, whereas C-control performs very robustly but long batch times may be required. SL-QDMC performs rather poorly even when there is no plant-model mismatch due to the high process nonlinearity, rendering successive linearization inaccurate. The NMPC strategy shows good overall robustness for two different control objectives, which were both within 7% of their optimal values, while satisfying all constraints on manipulated and state variables within the specified batch time. (C) 2009 American Institute of Chemical Engineers AIChE J, 55: 2631-2645, 2009
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