title: Elucidation of the crystal structure-physicochemical property relationship among polymorphs and hydrates of sitafloxacin, a novel fluoroquinolone antibiotic.
abstract: Physicochemical properties of two anhydrates (α-form and β-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 β-form exhibited the worst photostability than any other forms under the irradiation of a D65 lamp. The intramolecular hydrogen bonding in the β-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.
authors: Analytical & Quality Evaluation Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. suzuki.tetsuya.fb@daiichisankyo.co.jp
authors: Tetsuya
authors: T
authors: Suzuki
authors: Katsuhide
authors: K
authors: Terada
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D024841:Fluoroquinolones / Q000737:chemistry* / Q000528:radiation effects; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D010782:Photolysis; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*; D017155:Wettability
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D014867:Water; C076246:sitafloxacin