Novel Salt-Cocrystals of Berberine Hydrochloride with Aliphatic Dicarboxylic Acids: Odd-Even Alternation in Physicochemical Properties

In this study, various structurally similar aliphatic dicarboxylic acids, namely, succinic acid, glutaric acid, adipic acid, and pimelic acid, were employed as coformers to obtain phase pure cocrystals with berberine chloride (BCl) by a slow solvent evaporation method. The structures of the four novel salt-cocrystals of BCl were determined by single crystal X-ray diffraction analysis and their solid-state properties were characterized. Compared with BCl center dot 2H(2)O, all the cocrystals showed a higher melting point, improved powder dissolution and intrinsic dissolution rate (IDR), and lower hygroscopicity. It is noteworthy that the melting points and IDRs of these cocrystals exhibit an odd-even alternation with the carbon chain length of the acids.

Automated summary

This study utilized structurally similar aliphatic dicarboxylic acids as coformers to obtain phase pure cocrystals with berberine chloride through a slow solvent evaporation method. The cocrystals exhibited higher melting points, improved powder dissolution and intrinsic dissolution rate, and lower hygroscopicity compared to BCl·2H2O, with melting points and IDRs showing an odd-even alternation with the carbon chain length of the acids.