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

Abstract 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·3H 2 O by 4‐aminobenzoic acid. The two chloride ions and two water molecules derive from palmatine chloride constituted an R 4 4 (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.