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

International Journal of Pharmaceutics
2022.0

Abstract

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 NH...Cl(-) hydrogen bonds in BCl-4ABA and OH...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. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved.

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