Advances and future directions in morphology monitoring and control of organic crystals grown from solution

Abstract

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 on-line imaging and image analysis by reference to a case study of cooling crystallization of (L)-glutamic acid in a batch reactor. On-line imaging was found to be able to capture with high fidelity crystal shape and polymorphic transitions in real-time. The images were analyzed using a new multi-scale image analysis method to extract the crystals from the image background, and to calculate shape descriptors which were then used for shape recognition and deriving new monitoring charts showing the ratios of different polymorphs in real-time. Preliminary study on estimating crystal growth rates and kinetics parameters for different facets for needle shaped crystals was also presented. Finally a framework integrating morphology modeling, multi-dimensional population balance and computational fluid dynamics, with on-line 3D imaging and image analysis is presented which provides the basis for model predictive automatic control of the morphology of growing crystals.