Study of the preparation, characterization, and solubility of lidocaine complexed with 5-sulfosalicylic acid dihydrate.

Objective: This study was to prepare solid dispersions of lidocaine (Lid) with 5-sulfosalicylic acid dihydrate (SSA) by freeze-drying (freeze-dried [FD] Lid/SSA = 1/1) and to evaluate their physical properties.

Methods: Here, we evaluated the physicochemical properties and solubility of solid dispersions of Lid and SSA prepared by freeze-drying (freeze-dried [FD] Lid/SSA = 1/1).

Results: Differential scanning calorimetry measurements showed that after freeze-drying, the endothermic peak due to Lid melting, the dehydration peak, and the endothermic peak due to SSA melting disappeared. Powder X-ray diffraction results showed that the characteristic Lid and SSA peaks disappeared after freeze-drying, indicating a halo pattern. The near-infrared spectroscopy results suggested that Lid-derived -NH and -CH groups and the Lid-derived -OH and -CH groups from the SSA peak shifted and broadened after freeze-drying, suggesting their involvement in complex formation through Lid/SSA intermolecular interactions. Nuclear Overhauser effect spectroscopy-nuclear magnetic resonance (NMR) measurements showed a cross-peak due to the interaction between the Lid-derived -CH group and the SSA-derived -OH group, suggesting hydrogen bonding. Diffusion-ordered spectroscopy NMR measurements showed that the diffusion coefficients of Lid and SSA aggregated in FD Lid/SSA, suggesting a change in Lid dispersibility in the solvent owing to the formation of a complex with SSA. The solubility of FD Lid/SSA was approximately 88 mg/mL (∼20-fold higher than that of Lid).

Conclusions: These findings suggest that complex formation occurred in FD Lid/SSA; this enhanced the solubility of this dispersion.