Optimal seed recipe design for crystal size distribution control for batch cooling crystallisation processes

The paper presents a novel quality-by-design framework for the design of optimal seed recipes for batch cooling crystallization systems with the aim to produce a desired target crystal size distribution (CSD) of the product. The approach is based on a population balance modle-based optimal control framework, which optimsies the composites of seed blends, based on seed fractions that result from of moments and method of characteristics (QMOM-MOCH) approach for teh generic case of apparent size-dependent growth. Seed mixtures are represnted as a sum of Guassian distributions, where each Guassian corresopnds to the seed distribution in a particular sieve size range. The proposed methods are exemplified for the model system of potassium dichromate in water, for which is the paper also illustrates the simultaneous application of in situ process analytical tools, such as focused beam reflectance measurement (FBRM) for nucleation detection, attenuated total relection (ATR) UV/Vis spectorscopy for concentration monitoring, as wel as the in-line use of laser diffraction particle sizing for real-time CSD measurement. (C) 2010 Elsevier Ltd. All rights reserved.