Mechanochemical synthesis and solid-state characterization of molecular salts of pyridoxine: Vibrational spectroscopic and thermal consideration

Crystal engineering of multicomponent crystals offers opportunities for both generic active pharmaceutical ingredients (APIs) and innovative APIs (under patent protection) to be noncovalently bound with a wide range of organic compounds, forming new solid phases such as salts or cocrystals. These multicomponent crystals can enhance the physicochemical properties, processibility, and bioavailability of the APIs. The purpose of this research is to correlate vibrational (FTIR and Raman) spectroscopy studies with the thermal behavior of new molecular salts of the drug model pyridoxine (PN), using salt formers from the group of hydroxybenzoic acid derivatives known for their potent antioxidant activity. The coformers include syringic acid (SA) and ferulic acid (FA), synthesized through eco-friendly mechanochemical methods by treating bulk powders of their stoichiometric mixture with PN. The assigned vibrational modes and thermal behaviors of the pyridoxonium syringate (PN/SA) and pyridoxonium ferulate (PN/FA∙H2O) reveal the protonation of the pyridoxine N-atom in both salts structures. This protonation results in structural alterations in the crystal packing of the counterions, which exhibit unique spectral fingerprints and thermal profiles compared to the starting compounds.