Novel Cocrystal of Palmatine Chloride with Improved Hygroscopic Stability and Antimicrobial Potency: Experimental and Theoretical Studies

To highlight the benefits of the cocrystallization technique in enhancing the pharmaceutical characteristics and antimicrobial effect of palmatine chloride (PCl), a novel cocrystal of PCl with 4-aminobenzoic acid (AMA), abbreviated as PCl-AMA, is prepared to employ the combination of water-assisted grinding and solvent evaporation method. Single-crystal X-ray diffraction analysis displays that the formation of the PCl-AMA cocrystal results in the replacement of two water molecules in the crystal structure of PCl·3H₂O by 4-aminobenzoic acid. The two chloride ions and two water molecules derive from palmatine chloride constituted an R₄⁴(8) ring structure. Furthermore, two AMA chains are interconnected through the four-membered ring, continuously extending to form a parallel modular framework. The palmatine cations are arranged perpendicularly between the parallel modules, serving as a filling structure. This altered crystal structure imparted improved physicochemical properties to PCl, exhibiting enhanced moisture stability and reduced solubility. More intriguingly, the antimicrobial potency of the PCl-AMA cocrystal is enhanced owing to the auxiliary antibacterial effect of 4-aminobenzoic acid.