Improving solid-state properties of berberine chloride through forming a salt cocrystal with citric acid

Berberine chloride (BCl) can exist as an anhydrate, monohydrate, dihydrate, and tetrahydrate. Therefore, it faces the problem of humidity dependent solid phase change when environmental humidity varies during manufacturing and storage of berberine tablets. We have discovered a new 1:1 cocrystal formed between berberine chloride and citric acid (BCl-CA) that exhibits better stability against variations in humidity while maintaining similar thermal stability, solubility, dissolution rate, and tabletability. Thus, BCl-CA is a good alternative crystal form for use in formulation to manufacture berberine tablets.