Improvement of Solubility and Oral Bioavailability of 2-(N-Cyanoimino)-5{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) with Antidiabetic and Lipid-Lowering Activities in Dogs by 2-Hydroxypropyl-β-cyclodextrin
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- Hara Takumi
- Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Hirayama Fumitoshi
- Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Arima Hidetoshi
- Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Yamaguchi Yoshihiro
- Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Uekama Kaneto
- Graduate School of Pharmaceutical Sciences, Kumamoto University
書誌事項
- タイトル別名
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- Improvement of Solubility and Oral Bioavailability of 2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) with Antidiabetic and Lipid-Lowering Activities in Dogs by 2-Hydroxypropyl-.BETA.-cyclodextrin
- Improvement of Solubility and Oral Bioavailability of 2 N Cyanoimino 5 E 4 styrylbenzylidene 4 oxothiazolidine FPFS 410 with Antidiabetic and Lipid Lowering Activities in Dogs by 2 Hydroxypropyl ベータ cyclodextrin
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説明
2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) is a newly synthesized thiazolidine derivative having not only antidiabetic but also lipid-lowering activities. However, this compound has an extremely low aqueous solubility (2.8 (±0.33)×10−8 M (0.0094±0.0011 μg/ml) in 1.0 M phosphate buffer (pH 7.0) at 25 °C). In this study, we investigated the effect of various hydrophilic cyclodextrins (CyDs) on the solubility of FPFS-410 to select a CyD suitable for formulations of the compound. Among various CyDs, 2-hydroxypropyl-β-CyD (HP-β-CyD) had the highest solubilizing ability to FPFS-410, e.g., the solubility of the compound was increased 200000-fold by the addition of 40 mM HP-β-CyD, which was attributable to the formation of the 1 : 2 (guest : host) inclusion complexes. The interaction of HP-β-CyD with FPFS-410 was studied using 1H-nuclear magnetic resonance (NMR) spectroscopies including ROESY spectroscopy and a molecular modeling calculation. These results suggested that HP-β-CyD forms a 1 : 2 (guest : host) inclusion complex with FPFS-410 by including both the stilbene and thiazolidine moieties. FPFS-410/HP-β-CyD solid complexes with various stoichiometries were prepared by the spray drying and cogrinding methods, and confirmed by powder X-ray diffractometry that these complexes are in an amorphous state. The dissolution of FPFS-410 in water was significantly accelerated by the complexation with HP-β-CyD. In vivo studies revealed that HP-β-CyD markedly increases the bioavailability of FPFS-410 after oral administration in dogs. The present results suggest that HP-β-CyD is useful for improvement of the extremely low bioavailability of FPFS-410.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 54 (3), 344-349, 2006
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679148095360
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- NII論文ID
- 110004820390
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 7830118
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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