Multi-scale segmentation image analysis for the in-process monitoring of particle shape with batch crystallisers

The morphological forms and habits of pharmaceutical crystals are important properties that can be affected by minor changes in operating conditions such as cooling rates and supersaturation. As a result the pharmaceutical industry demands on-line techniques for real-time measurement of the dynamic changes of these properties in crystallisers. On-line imaging represents a potentially powerful technique for real-time monitoring of the morphological forms during crystal growth, but a major challenge is the availability of methods for image analysis that need to be tolerant to the quality of on-line images, accurate, fast and robust. This paper describes a multi-scale segmentation methodology for analysis of images obtained for batch cooling crystallisation of (L)-glutamic acid using an on-line high-speed imaging system developed by the pharmaceutical manufacturer GlaxoSmithKline. The method proves to be able to analyse effectively the on-line images of different crystal morphological forms, and of varied qualities. Application of the methodology to the analysis of images from a different on-line imaging probe and from an off-line slurry sample imaging system demonstrated the capability of generalisation of the method.