Characterization of the solubility and solid-state properties of saccharin salts of fluoroquinolones.
Saccharinates salts of the fluoroquinolone antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as pure crystalline anhydrous solids with sweet taste. The products were characterized by one- ((13)C) and two-dimensional ((1)H-(13)C) dimensions solid state Nuclear Magnetic Resonance and infrared spectroscopy showing ionic interactions between the saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings were also identified. Thermal behavior and powder X-ray diffraction provided complementary evidences of salt formation. The series of products showed improved properties with respect to water solubility. A solubility model was developed. These salts would be a good way forward to developing more suitable formulations of these APIs.
Romañuk
Carolina B
CB
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina.
Manzo
Ruben H
RH
Linck
Yamila Garro
YG
Chattah
Ana K
AK
Monti
Gustavo A
GA
Olivera
Maria E
ME
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004055:Differential Thermal Analysis; D024841:Fluoroquinolones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012439:Saccharin / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012439:Saccharin