Five solvates of a multicomponent pharmaceutical salt formed by berberine and diclofenac

A multicomponent pharmaceutical salt formed by the isoquinoline alkaloid berberine (5,6-dihydro-9,10-dimethoxybenzo[ g ]-1,3-benzodioxolo[5,6- a ]quinolizinium, BBR) and the nonsteroidal anti-inflammatory drug diclofenac {2-[2-(2,6-dichloroanilino)phenyl]acetic acid, DIC} was discovered. Five solvates of the pharmaceutical salt form were obtained by solid-form screening. These five multicomponent solvates are the dihydrate (BBR–DIC·2H 2 O or C 20 H 18 NO 4 + ·C 14 H 10 Cl 2 NO 2 − ·2H 2 O), the dichloromethane hemisolvate dihydrate (BBR–DIC·0.5CH 2 Cl 2 ·2H 2 O or C 20 H 18 NO 4 + ·C 14 H 10 Cl 2 NO 2 − ·0.5CH 2 Cl 2 ·2H 2 O), the ethanol monosolvate (BBR–DIC·C 2 H 5 OH or C 20 H 18 NO 4 + ·C 14 H 10 Cl 2 NO 2 − ·C 2 H 5 OH), the methanol monosolvate (BBR–DIC·CH 3 OH or C 20 H 18 NO 4 + ·C 14 H 10 Cl 2 NO 2 − ·CH 3 OH) and the methanol disolvate (BBR–DIC·2CH 3 OH or C 20 H 18 NO 4 + ·C 14 H 10 Cl 2 NO 2 − ·2CH 3 OH), and their crystal structures were determined. All five solvates of BBR–DIC (1:1 molar ratio) were crystallized from different organic solvents. Solvent molecules in a pharmaceutical salt are essential components for the formation of crystalline structures and stabilization of the crystal lattices. These solvates have strong intermolecular O...H hydrogen bonds between the DIC anions and solvent molecules. The intermolecular hydrogen-bond interactions were visualized by two-dimensional fingerprint plots. All the multicomponent solvates contained intramolecular N—H...O hydrogen bonds. Various π–π interactions dominate the packing structures of the solvates.