Crystal Structure Analysis of Pharmaceuticals with Electron Diffraction

X-Ray powder diffraction (XRPD) has already successfully been used for a long time in the field of pharmaceuticals for polymorph screening (fingerprinting) and more recently for the structural and microstructural analysis of active pharmaceutical ingredients (API) and excipients.Large enough single crystals are in fact either very difficult to growth or do not represent well the properties of the polycrystalline pharmaceutical compounds. Furthermore, quantitative phase analyses can only be performed with powder materials. Although XRPD is well established, there are often limitations in its successful application, in particular when facing complex structures whose XRPD patterns are characterized by many overlapping peaks and the determination of the cell parameters and the extraction of the diffracted intensity is very difficult and often unsuccessful. In such cases the use of synchrotron radiation and advanced experimental methods need to be explored (e.g. texture method [1], anisotropic thermal expansion [2]) but the determination of the crystal structure is never guaranteed and far from being routine.