On-Line Measurement of The Shape and Growth Rates of Organic Crystals in Reactors: Advances and Perspectives for Control

Organic crystals grown from solution are known to exhibit multiple morphology and habits which are of great importance to the end use property of the product such as the bioavailability and down stream processing such as in filtration and drying. The crystal morphology can also dictate other quality measures such as the size. This paper reviews recent developments in on-line crystal morphology measurement and control using various techniques including on-line imaging and image analysis, and XRD. On-line imaging was found to be the most promising technique in capturing with high fidelity crystal shape and polymorphic transitions in real-time. Process in imaging and image analysis techniques will also be reviewed for extracting the crystals from the image background especially for images with uneven background intensity, of needle-like crystals and of high concentration slurries. Discussion will be given to shape descriptors and automatic shape recognition. Preliminary results and challenges for estimating crystal growth rates and kinetics parameters for different crystal facets will also be discussed. Future research directions for obtaining 3D instead of 2D dimensional information using imaging and image analysis techniques will be explored. Finally a framework integrating morphology modeling, multi-dimensional population balance and computational fluid dynamics, with 3D imaging and image analysis will be presented which provides the basis for model predictive automatic control of the morphology of growing crystals