Influence of the crystallisation approach on multicomponent systems of palmatine chloride

Abstract

Cocrystallization and salt formation are effective approaches to alter a drug's physicochemical properties. By understanding the hydrogen bond strategies involved in synthon formation, a multicomponent system can be designed and developed. In the current study, palmatine chloride (PLT-Cl) was cocrystallized with coformers like gallic acid (GAL), gentisic acid (GEN) and pamoic acid (PAM), which contain carboxylic acid and hydroxyl groups in their structures. PLT-Cl is an isoquinoline alkaloid containing a quaternary ammonium cation and a chloride anion. GAL and PAM replaced the chloride ion from the crystal lattice and formed a salt with PLT. Therefore, hydrogen bonds like O–H⋯O and C–H⋯O interactions were predominantly seen in the crystal structure. GEN exists as a neutral molecule and retains the chloride ion in the crystal lattice, leading to the formation of intermolecular interactions with PLT-Cl. The C–H⋯Cl⁻, C–H⋯O, O–H⋯Cl⁻ and O–H⋯O hydrogen bond interactions aided in constructing the three-dimensional crystal structure of PLT–GEN. By developing new multicomponent systems with GAL, GEN and PAM, this study attempts to understand the circumstances which contribute to the formation of new salts with or without the Cl ion in the crystal lattice. The implementation of coformers (GAL/GEN/PAM) in the PLT-Cl crystal structure has reduced the solubility of PLT-Cl and exhibits a slow drug release profile.