Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Four lidocaine molecular salts of
dicarboxylic acids (oxalic, fumaric,
malonic, and succinic) were synthesized and characterized by a combined
use of X-ray powder and single-crystal diffraction, differential scanning
calorimetry, Fourier transform infrared spectroscopy (FT-IR), and
solid-state NMR (1H MAS and CRAMPS, and 13C
and 15N CPMAS): all molecular salts show a dramatic increase
in their melting point with respect to both lidocaine and lidocaine
hydrochloride, and a higher dissolution rate and thermodynamic solubility
in physiological solution with respect to the free base.