Real‐time product morphology monitoring in crystallization using imaging technique

Abstract Many speciality organic chemical products, such as pharmaceuticals are crystals that exhibit multiple morphological forms and habits that are of critical importance not only to the end use properties of the products, but also to their downstream processing, such as in filtration and handling and in transport and storage. It is known that minor changes in operating conditions, such as cooling rates and supesaturation can have significant impact on the product leading to batch‐to‐batch variation. As a result, precision manufacture of crystalline products demands on‐line techniques for real‐time measurement of crystal morphology. The use of a non‐invasive on‐line imaging technique in a batch reactor for monitoring cooling crystallization of (L)‐glutamic acid which exhibits two polymorphs, alpha and beta is described. The technique was found to allow real‐time observation of some temporal moments that are critical in the crystallization process, in particular the crystallization onset and transformation between the two polymorphs. For validation and benchmarking purpose, an off‐line system for particle characterization, the PharmaVision 830, and photo‐microscope were also used in the study in parallel with the on‐line imaging system. © 2005 American Institute of Chemical Engineers AIChE J, 2005