Modulating Pharmaceutical Properties of Berberine Chloride through Cocrystallization with Benzendiol Isomers.

Abstract

To synthesize and characterize new cocrystals of berberine chloride (BCl) for potential pharmaceutical tablet formulation. Solutions of BCl with each of three selected cocrystal formers, catechol (CAT), resorcinol (RES), and hydroquinone (HYQ) were slowly evaporated at room temperature to obtain crystals. Crystal structures were solved using single crystal X-ray diffraction. Bulk powders were characterized by powder X-ray diffraction, thermogravimetric-differential scanning calorimetry, FTIR, dynamic moisture sorption, and dissolution (both intrinsic and powder). Single crystal structures confirmed the formation of cocrystals with all three coformers, which revealed various intermolecular interactions that stabilized crystal lattices, including O-H···Cl- hydrogen bonds. All three cocrystals exhibited better stability against high humidity (up to 95% relative humidity) at 25 ℃ and higher intrinsic and powder dissolution rates than BCl. The enhanced pharmaceutical properties of all three cocrystals, ascompared to BCl, further contribute to the existing evidence that confirms the beneficial role of cocrystallization in facilitating drug development. These new cocrystals expand the structure landscape of BCl solid forms, which is important for future analysis to establish a reliable relationship between crystal structure and pharmaceutical properties.