Elucidation of the crystal structure-physicochemical property relationship among polymorphs and hydrates of sitafloxacin, a novel fluoroquinolone antibiotic

作者：Suzuki Tetsuya^*; Terada Katsuhide

来源：International Journal of Pharmaceutics, 2012, 422(1-2): 1-8.

DOI：10.1016/j.ijpharm.2011.10.001

• Quinolone
• Antibiotics
• Hygroscopicity
• Photostability
• Solubility
• Crystal structure-physicochemical property relationship

Physicochemical properties of two anhydrates (alpha-form and beta-form) and three hydrates (hemihydrate, monohydrate and sesquihydrate) of sitafloxacin (STFX), a novel fluoroquinolone antibiotic, were investigated and correlated with the crystal structure of each crystalline form. STFX sesquihydrate showed larger weight change between 1% and 95% relative humidities (RHs) than other crystalline forms. In the crystal of sesquihydrate, STFX molecules form a channel structure where water molecules exist. Contrary to sesquihydrate, water molecules in a monohydrate are located in well-defined and isolated crystallographic sites. The beta-form exhibited the worst photostability than any other forms under the irradiation of a D65 lamp. The intramolecular hydrogen bonding in the beta-form caused a red shift on the solid-state UV spectrum by prolonging the conjugation system of the quinolone ring, resulting in greater absorption of photoenergy and consequent degradation. Solubility is also affected by the crystalline structure. Standard free energy of the formation of STFX molecule in each crystalline form and/or lattice energy binding STFX molecules to retain the crystal structure might cause a difference in solubility.

• 出版日期2012-1-17