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

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

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

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

Using Salt Cocrystals to Improve the Solubility of Niclosamide

This Article reports the solvent-free synthesis and characterization of a number of different crystal forms of niclosamide (HNic), which is an API belonging to the Salicilamide class. The synthesized compounds are four new salt cocrystals (<b>KNic·HNic·H₂O</b>, <b>KNic·HNic·3H₂O</b>, <b>NaNic·HNic·3H₂O</b>, <b>NaNic·HNic·2H₂O</b>), a classic cocrystal with imidazole (IM) (<b>HNic·IM</b>), and two sodium salts, (<b>NaNic·DMSO·H₂O</b> and <b>NaNic·DMSO·2H₂O</b>). The peculiarity of these salt cocrystals is the API’s concomitant presence as both a neutral component and as a salt coformer and the fact that they interact via hydrogen bond formation. HNic’s poor aqueous solubility makes the enhancement of its dissolution rate via the modulation of its physical properties extremely important. All samples have been investigated using a combination of solid-state experimental techniques which provide complementary information on powdered samples. These techniques are X-ray powder diffraction, solid-state NMR, IR, and Raman. Single crystals were only obtained for <b>KNic·HNic·H₂O</b> and <b>NaNic·DMSO·2H₂O</b>. The nature of the adducts (whether salt or cocrystal), their stoichiometry and the presence of independent molecules in the unit cell of the other samples were thus all determined by means of solid-state NMR and the comparative analysis of ¹³C and ¹⁵N CPMAS (Cross-Polarization Magic Angle Spinning) and ¹H MAS spectra. Furthermore, differential scanning calorimetry, thermogravimetric analysis and intrinsic dissolution rate measurements completed the characterization and enabled us to evaluate the effects of microscopic changes (molecular packing, weak interactions, conformations, etc.) on the macroscopic properties (thermal stability and bioavailability) of the multicomponent forms. The results obtained indicate that the formation of salt cocrystals provides a reliable method with which to improve the HNic intrinsic dissolution rate

Isomorphous Salts of Anti-HIV Saquinavir Mesylate: Exploring the Effect of Anion-Exchange on Its Solid-State and Dissolution Properties

Saquinavir (SQV) is an important protease inhibitor used for AIDS/HIV antiretroviral therapy. As a free base it is almost insoluble in water, and it is commercialized as its mesylate salt (SQVM), classified as belonging to class IV (low permeability and solubility). Anion exchange has been used in this work to explore the effect of halides replacing the mesylate anion on the solid state and solubility properties of saquinavir at ambient temperature. All solid forms obtained were characterized via X-ray single crystal and powder diffraction, and their thermal behavior was analyzed via differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy and variable temperature X-ray powder diffraction. Saquinavir chloride (SQVCl), saquinavir bromide (SQVBr), and saquinavir iodide (SQVI) are all hydrates, the difference in the anion size being responsible for the different number of water molecules (3, 2, and 1, respectively). Dissolution properties have also been investigated, and it has been found that the behavior in water of SQVM and SQVCl are very similar, with 43 and 38% dissolved in 90 min, respectively, whereas for SQVBr and SQVI this percentage was 31 and 18%, respectively. Solid SQVCl could therefore be used as a valid alternative to current pharmaceutical formulations