Abstract
d-Mannitol is a typical polymorphic crystalline compound. In this paper, this polymorphic transformation from the α to the β form of mannitol is monitored by in situ Raman spectroscopy, focused beam reflectance measurement (FBRM) and particle vision measurement (PVM). The standard Raman spectra of the two polymorphs of mannitol were determined and the characteristic peaks for the different polymorphs were chosen to track the transformation process. By combining Raman with FBRM and PVM, relationships between fine particles and metastable form dissolution and also between coarse particles and stable form crystallization could be defined. The solution-mediated polymorphic transformation mechanism was confirmed by these in situ tools. The effect of temperature, solvent and substrate mass on the transformation time was also investigated. It was noted that operating temperature and solvent composition have a significant influence on the transformation time.
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