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·2H₂O or C₂₀H₁₈NO₄⁺·C₁₄H₁₀Cl₂NO₂^-·2H₂O), the dichloromethane hemisolvate dihydrate (BBR-DIC·0.5CH₂Cl₂·2H₂O or C₂₀H₁₈NO₄⁺·C₁₄H₁₀Cl₂NO₂^-·0.5CH₂Cl₂·2H₂O), the ethanol monosolvate (BBR-DIC·C₂H₅OH or C₂₀H₁₈NO₄⁺·C₁₄H₁₀Cl₂NO₂^-·C₂H₅OH), the methanol monosolvate (BBR-DIC·CH₃OH or C₂₀H₁₈NO₄⁺·C₁₄H₁₀Cl₂NO₂^-·CH₃OH) and the methanol disolvate (BBR-DIC·2CH₃OH or C₂₀H₁₈NO₄⁺·C₁₄H₁₀Cl₂NO₂^-·2CH₃OH), 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.