New multicomponent crystals of mequitazine (MQZ) with succinic acid (SUC), fumaric acid (FUM), glycolic acid (GLC), and glycolamide (GLA) were obtained after liquidassisted grinding. The hydrate/anhydrate availability in the crystals differed owing to slight differences in the coformer structure. Therefore, the causes of these differences in the crystal structure were investigated. The structures of crystals, for which single crystals were difficult to obtain, were obtained using powder diffraction crystal structure analyses. The crystal structures, including the disordered structure and the structure in which the H atom position could not be identified, were validated via dispersion-corrected density functional theory calculations using the Quantum ESPRESSO code. MQZ-SUC and MQZ-FUM formed isostructural anhydrates, but only MQZ-SUC formed a hydrate by twisting the alkyl straight chain; hence, the difference between the dihedral angles that the coformer can form led to a small change in polymorphism. MQZ-GLC hydrate and MQZ-GLA anhydrate had no isomorphic crystals, MQZ-GLC formed a hydrate, and MQZ-GLA formed an anhydrate. Differences in the number of hydrogen bond donors in the coformer led to major changes in polymorphism. The results of this study might be useful for coformer selection and controlling multicomponent crystal polymorphism.

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The structural transition behaviors of the hydration and dehydration of mequitazine glycolate (MQZ-GLC) after exposure to heat and relative humidity have yet not been clarified, although our previous study demonstrated...