Investigation of Physical Properties of Disodium Etidronate Tetrahydrate and Application of Phosphorus K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy
Investigation of Physical Properties of Disodium Etidronate Tetrahydrate and Application of Phosphorus K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy
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四水依替膦酸二钠的物理性质研究及磷K边X射线吸收近边结构光谱的应用
DOI：
10.1007/s11095-021-03151-4
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发表时间：
2021
影响因子：
3.7
通讯作者：
Noguchi Shuji
中科院分区：
文献类型：
--
作者：
Ito Naoya;Hashizuka Takahiko;Ito Masataka;Suzuki Hironori;Noguchi Shuji
二羟乙膦酸盐是一种双膦酸盐，广泛用于治疗骨质疏松症和佩吉特病等骨疾病。方法采用X射线粉末衍射（XRPD）、热分析、动态水蒸气吸附（DVS）、X射线单晶结构分析、磷K边X射线吸收近边结构（XANES）等方法，首次研究了依替膦酸二钠四水合物晶型I的物理性质。通过加热转化为晶型II，最后转化为晶型III。DVS测量显示，无定形形式、形式II和形式III通过加湿再水合为形式I，并且形式I甚至在0%相对湿度下稳定。这些结果表明，I型在环境条件下是最稳定的固态，并且适合作为API用于以固体制剂生产。磷的K-边XANES光谱在形式I、无定形形式和形式II之间不同，这可以归因于磷酸盐部分和钠离子之间的配位键方案的差异。结果表明，磷K-边XANES光谱可以应用于鉴定或含磷酸盐moiets.ConclusionsAcquired有关物理性质的信息的API的晶型的歧视是至关重要的固体制剂的依替膦酸二钠的制造。XANES光谱是一种很有前途的替代方法，用于评估固态形式的原料药。
PurposeDisodium etidronate is a bisphosphonate, compounds that are widely used in the treatment of bone disorders such as osteoporosis and Paget’s disease. We investigated the physical properties of disodium etidronate tetrahydrate crystal, form I.MethodsWe used X-ray powder diffraction (XRPD), thermal analysis, dynamic vapor sorption (DVS), X-ray single crystal structure analysis, and phosphorus K-edge X-ray absorption near-edge structure (XANES) spectroscopy for the first time.ResultsXRPD and thermal analyses demonstrated that form I was dehydrated and transformed to an amorphous form, to a crystalline form II, and finally to a form III by heating. DVS measurements revealed that the amorphous form, form II, and form III were rehydrated to form I by humidification, and form I was stable even at 0% relative humidity. These results indicate that form I is the most stable solid-state under ambient conditions and is suitable as an API for manufacture in solid formulations. The phosphorus K-edge XANES spectra differed among form I, the amorphous form, and form II, which may be ascribed to the difference in the coordinate bond schemes between the phosphate moieties and sodium ions. The results demonstrated that the phosphorus K-edge XANES spectroscopy could be applied to the identification or the discrimination of crystal forms of the APIs containing phosphate moieties.ConclusionsAcquired information about physical properties are crucial for manufacturing of solid formulations of disodium etidronate. XANES spectroscopy is a promising alternative method for evaluating the solid-state forms of APIs.
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依替膦酸的历史。
影响因子：
4.1
作者：
Nelson B. Watts;Charles H. Chesnut;H. Genant;Steven T. Harris;R. Jackson;Angelo A. Licata;Paul D. Miller;W. Mysiw;B. Richmond;D. Valent
通讯作者：
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影响因子：
2.5
作者：
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影响因子：
4.4
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.8
作者：
Ito Masataka;Suzuki Hironori;Noguchi Shuji
通讯作者：
Noguchi Shuji