Structural Transformations of D-Mannitol Induced by in Situ Milling Using Real Time Powder Synchrotron Radiation Diffraction

We have investigated the solid-state transformation of anhydrous beta-D-mannitol upon milling using synchrotron X-ray powder diffraction. The 1720 diffraction patterns, collected in real time during the operation of the mill (6 h), have been analyzed by sequential Rietveld refinements. From this analysis we confirm that a polymorphic conversion has occurred from the form beta toward the form alpha. Moreover, the quantification and the microstructural analysis of both polymorphs have allowed obtaining new results: (i) the kinetic of the transformation is characterized by a sigmoidal shape, (ii) little microstructural evolution occurs during the solid-state transformation, (iii) no intermediate amorphous phase, preceding the transformation toward the metastable crystalline alpha phase, can be detected. A comparison in depth of the two crystal structures is given, and two models are proposed in order to explain this direct conversion beta -> alpha.