Structure elucidation of olanzapine molecular salts by combining mechanochemistry and MicroED

Olanzapine (OLN), an anti-psychotic drug, is one of the most widely studied pharmaceutical materials. Although OLN and most of their multicomponent solids are highly crystalline, some of their molecular salts are difficult to crystallize and optimization takes long time. After several batches of failed crystallization, we applied mechanochemistry and microcrystal electron diffraction (MicroED) for structure elucidation. This combined approach was successful not only in structure determination of the drug molecule but also in characterizing traces of impurity present in a bulk solid. This study demonstrates that the combined approach is fast and efficient for structure elucidation of pharmaceutical materials when generation of suitable single crystals is challenging.