Structural Analysis of Active Pharmaceutical Ingredients in Tablets Using 3D ED/MicroED

In this study, we report on the direct confirmation of crystal structure and conformation of API in tablets by 3D ED/MicroED. Allegra, Clarith, and Ibrance tablets were selected for this study. The crystal structures and conformations were analyzed in detail to determine whether there were any changes in the polymorphism of the API crystals during the formulation process. As a result, it was confirmed that the crystal polymorphs of Allegra (fexofenadine hydrochloride, Form I) and Clarith (clarithromycin, Form II) were unchanged. These results directly confirm that there has been no change in crystal polymorphism during the formulation process of Allegra and Clarith. For the Ibrance tablet (palbociclib Form A), a slight shrinkage of the crystal lattice was observed, which showed that 3D ED/MicroED allows us to capture the slight changes in the crystal structure. In addition, this is the first report of crystal structure elucidation of fexofenadine hydrochloride Form I and palbociclib Form A by single-crystal structure analysis. These results were obtained from randomly selected crystals using the "selected area electron diffraction method", which is one of the outstanding features of 3D ED/MicroED.