title: Solid-state variation of troglitazone drug substance by using a different recrystallization method.
abstract: Rapid and slow crystallization methods (A and B) were applied for troglitazone, an equal mixture of four stereoisomers. Differences in the powder x-ray diffractometry patterns and hygroscopic patterns were observed among the samples crystallized by these methods, suggesting that troglitazone has solid-state variation. In this article, troglitazone recrystallized by method A was evaluated to clarify its structural characteristics and physical property. The crystal structure of predried troglitazone recrystallized by method A was proved to be a dihydrate. By drying, it changed reversibly to an anhydrate, which is the same structure as the RS/SR form, keeping the same enantiomer ratio. The solubility of the troglitazone by method A higher than that by method B at all enantiomer levels. But making the troglitazone amorphous equalized the enantiomeric solubilities of the substances by both methods as well as increased the intrinsic solubilities. Troglitazone by both methods was proved to be stable and retained the ratio of the stereoisomers.
authors.affiliation: Product Development Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan. nobuyu@shina.sankyo.co.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Ko
authors.initials: K
authors.lastname: Kasahara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Suzue
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Takao
authors.initials: T
authors.lastname: Kawasaki
mesh_terms: D000327:Adsorption; D002839:Chromans / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004304:Dosage Forms / Q000592:standards; D004345:Drug Industry / Q000379:methods / Q000639:trends; D004355:Drug Stability; D008854:Microscopy, Electron / Q000379:methods; D015394:Molecular Structure; D012995:Solubility; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism; D045162:Thiazolidinediones / Q000737:chemistry*; D000077288:Troglitazone; D017155:Wettability; D014961:X-Ray Diffraction / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D002839:Chromans; D004304:Dosage Forms; D045162:Thiazolidinediones; D000077288:Troglitazone