(70dg) Visualization of Polymorphic Crystallization in Working Reactor Using in-Process Diffraction Tomography
AIChE Spring Meeting and Global Congress on Process Safety
Monday, April 24, 2006 - 4:30pm to 8:30pm
A major challenge in the preparation of pharmaceutical solid compounds is to maintain the routine production of target materials in a specified polymorphic form, Polymorphism in organic materials has driven interest in the application of process analytical technology to understand both the causes and progression of polymorphism in real process reaction system with the longer term goal of controlling polymorphism during manufacture.
TEDDI (Tomographic Energy-Dispersive Diffraction Imaging) at Daresbury Synchrotron Radiation Source (SRS), provides a novel technique of non-destructively exploring for the structural and chemical content of individual volume elements (typically 10-4-10 mm3) within bulk systems, through the energy-dispersive diffraction of intense hard white X-ray beams produced by synchrotron. This has been used in the research work for directly mapping the spatial distribution of polymorphic contents within a working reactor and changes to it as a function of variation of processing parameters (agitation rate, temperature profile, reactor scale size etc.) by intelligently scanning the sample. The experimental material chosen for this work was glutamic acid crystallized in a model jacket-heated vessel with a magnetic flea stirrer at the base. Distribution and orientation of á & â form crystals at post crystallization state in the vessel were studied, and crystallization was mapped during cooling crystallization process. The new technical development of detection using area detector combined with multi-channel collimator provides the potential of real-time mapping for crystal formation and progression distributed in a crystallization reactor.