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 power and single-crystal diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and solid-state NMR (H-1 MAS and CRAMPS, and C-13 and N-15 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.