title: Four new polymorphic forms of suplatast tosilate.
abstract: We found four new polymorphic forms (γ-, ε-, ζ-, and η-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (α-, β-, and δ-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the ε- and η-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the ε- and η-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The α-form was the most insoluble in 2-propanol at 35°C, and was thus concluded to be the most stable form. The ε-form was the most soluble, and a polymorphic transition from the ε- to the α-form was observed during solubility testing.
authors.affiliation: Taiho Pharmaceutical Co. Ltd., Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: kei-nagai@taiho.co.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Ace Japan Co. Ltd., Higashine-koh, Higashine, Yamagata 999-3701, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ushio
authors.affiliation: Taiho Pharmaceutical Co. Ltd., Kamikawa-machi, Kodama-gun, Saitama 367-0241, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Miura
authors.affiliation: RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D018926:Anti-Allergic Agents / Q000737:chemistry*; D001190:Arylsulfonates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy; D033362:Powder Diffraction; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013452:Sulfonium Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D013452:Sulfonium Compounds; C073028:suplatast tosilate
keywords: Physicochemical properties; Polymorphs; Rietveld refinement; Seeding analogous compounds; Solubility; Suplatast tosilate