Complex Formation of Nitrazepam in Coprecipitating and in Co-grinding with Methylated β-Cyclodextrins
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概要
- 論文の詳細を見る
Complex formation of nitrazepam with heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DM)-β-CyD) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CyD) together with α-, β-, and γ-cyclodextrins (CyDs) in aqueous solution was confirmed by the solubility method. A_L type phase solubility diagrams were obtained in all cases. The highest stability constant and the highest solubilized amount of nitrazepam was obtained with DM-β-CyD, in the order DM-β-CyD>β-CyD>TM-β-CyD>γ-CyD>α-CyD. Coplex formation of nitrazepam with DM-β-CyD and TM-β-CyD in the solid state was assessed by differential scanning calorimetry (DSC), infrared (IR) spectroscopy and X-ray diffractometry. Crystalline inclusion complex of nitrazepam with DM-β-CyD in 1 : 2 molar ratio was botained by the coprecipitation method. X-Ray diffraction analyses explained that nitrazepam was transformed from the crystalline to non-crystalline (amorphous) state by grinding with methylated β-CyDs. DSC analyses revealed that the heat of fusion due to nitrazepam disappeared in the ground ixture and coprecipitate of nitrazepam with DM-β-CyD in 1 : 2 molar ratio, which demonstrated the optimum content of dispersal nitrazepam with DM-β-CyD in the solid state. IR spectra showed that there were higher frequency shifts for the carbonyl stretching band of nitrazepam in the ground mixtures and coprecipitates of DM-β-CyD and TM-β-CyD similar to the case of nitrazepam in CHCl_3 solution, which were considered due to the monomolecular dispersion of nitrazepam in a hydrophobic environment.
- 社団法人日本薬学会の論文
- 1990-12-25
著者
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山本 恵司
千葉大学大学院薬学研究院製剤工学研究室
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山本 恵司
Faculty of Pharmaceutical Sciences, Chiba University
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仲井 由宣
Faculty of Pharmaceutical Sciences, Chiba University
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仲井 由宣
千葉大学薬学部
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AHMED Mahrous
Faculty of Pharmaceutical Sciences, Chiba University
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ABOUTALEB Ahmed
Faculty of Pharmacy, Assiut University
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RAHMAN Aly
Faculty of Pharmacy, Assiut University
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SALEH Saleh
Faculty of Pharmacy, Assiut University
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仲井 由宣
Tsumura And Co. Ibaraki Jpn
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仲井 由宣
Faculty Of Pharmaceutical Science Chiba University
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Rahman Aly
Faculty Of Pharmacy Assiut University
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Aboutaleb A
Faculty Of Pharmacy Assiut University
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Aboutaleb Ahmed
Faculty Of Pharmacy Assiut University
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Ahmed M
Faculty Of Pharmaceutical Sciences Chiba University
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Ahmed Mahrous
Faculty Of Pharmaceutical Sciences Chiba University
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Saleh S
Faculty Of Pharmacy Assiut University
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山本 恵司
Faculty Of Pharmaceutical Sciences Chiba University
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Saleh Saleh
Faculty Of Pharmacy Assiut University
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