Complexation with aromatic carboxylic acids expands the solid-state landscape of berberine

Two novel salt cocrystals of berberine chloride (BCl) with 4-aminobenzoic acid (BCl-4ABA) and 4-hydroxybenzoic acid (BCl-4HBA) and one new berberine salt with 2,6-dihydroxybenzoic acid (B)(+)(26DHBA)(-) were prepared and characterized. The chloride anions form N-H center dot center dot center dot Cl- hydrogen bonds in BCl-4ABA and O-H center dot center dot center dot Cl- hydrogen bonds in BCl-4HBA. In (B)(+)(26DHBA)(-), the ionic interactions between 26DHBA(-) and quaternary ammonium cation of berberine contribute to a stronger crystal lattice and a higher melting point. All three new crystal forms exhibit a lower hygroscopicity at 25 degrees C than BCl, which is the crystal form used in the commercial tablets. Compared to BCl, the dissolution rates of BCl-4ABA and BCl-4HBA in water are higher but that of (B)(+)(26DHBA)(-) is lower. Among the three crystal forms, the form with a higher melting point also exhibits a lower dissolution rate, which is explained by the stronger intermolecular interactions in these crystals.

Automated summary

This study prepared and characterized new crystal forms of berberine chloride with different organic acids. The new crystal forms exhibited lower hygroscopicity and higher melting points, with the crystal form having stronger ionic interactions with the quaternary ammonium cation showing higher melting point and lower dissolution rate.