Classifying organic crystals via in-process image analysis and the use of monitoring charts to follow polymorphic and morphological changes

The polymorphic and morphological forms, and growth rates of different crystal facets are important parameters in pharmaceutical crystallisation processes that call for techniques for their real-time monitoring. In this paper, we describe a method for real-time classification of crystal polymorphic and morphological forms based on on-line imaging and image analysis. The focus of discussion is on deriving quantitative shape descriptors from images obtained on-line in real-time, automatic classification of crystals, the estimation of ratios of different polymorphs and new monitoring charts showing the relative average growth rates of facets of crystals. The work presented is based on experimental results of crystallisation in a batch reactor of (L)-glutamic acid that has two polymorphs, the prismatic alpha and needle-shaped beta forms.