Application of In-Process X-ray Powder Diffraction for the Identification of Polymorphic Forms during Batch Crystallization Reactions

Abstract

An on-line X-ray diffraction system capable of monitoring and identifying the polymorphic form of organic materials crystallized during batch crystallization processes is described. The overall system comprises a conventional X-ray source, monochromator, collimator, slits, curved position sensitive detector, and a flow-through analysis cell together with the electronics and the data acquisition software. The cell enables X-ray diffraction data to be recorded from crystals suspended within a slurry pumped to and from a batch crystallizer via an external temperature controlled sampling loop. The system is validated via benchmark crystallization studies of urea, l-glutamic acid and monosodium glutamate. The system was found to have a performance consistent with a lower detection limit of ca. 1% wt % of crystals and to be able to follow polymorphic transformation during representative crystallization processes. A forward look to the further development of the system is provided.