Effect of environmental temperature on polymorphic solid-state transformation of indomethacin during grinding.
Effect of environmental temperature on polymorphic solid-state transformation of indomethacin during grinding.
复制标题
环境温度对吲哚美辛研磨过程中多晶型固态转变的影响
DOI：
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发表时间：
1986
影响因子：
1.7
通讯作者：
N. Kaneniwa
中科院分区：
文献类型：
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作者：
M. Otsuka;Takahiro Matsumoto;N. Kaneniwa
采用X射线衍射分析、红外光谱和差示扫描量热法研究了玛瑙离心球磨机在200 rpm转速下研磨对吲哚美辛（IMC）多晶型物理化性质的影响。在4°C和30±0.5°C下研磨α和γ晶型（亚稳和稳定晶型）IMC，用X射线衍射内标法测定研磨产物的结晶度（Xc），结果表明，γ晶型IMC的Xc随研磨时间的延长而降低，4 h后Xc为0%，即γ晶型IMC已转化为非晶态固体。在30°C下研磨1 h后，约45%的γ型IMC转化为非晶固体，而研磨10 h后的产物转化为α型IMC;在4°C下研磨2 h后的α型IMC的Xc为0，即α型IMC在4°C下2 h内转化为非晶固体。在30°C下研磨的α晶型的Xc随研磨时间的延长而降低，10 h后的Xc值约为60%;在35°C下研磨的γ晶型在4°C下研磨10 h后的溶解度比完整的γ晶型大约60%。在30°C、4°C和30 ° C下，γ型溶出度为0.94 mg/100 ml，α型溶出度为0.94 mg/100 ml，与α型溶出度相当。
The effect of grinding in an agate centrifugal ball mill at 200 rpm on the physicochemical properties of indomethacin (IMC) polymorphs was studied by means of X-ray diffraction analysis, infrared spectroscopy and differential scanning calorimetry. The α and γ forms (metastable and stable forms) of IMC were ground at 4°C ant at 30±0.5°C, and the degree of crystallinity (Xc) of the ground products was measured by the X-ray diffractional internal standard method.The Xc of the γ form ground at 4°C decreased with increasing grinding time, and was 0% after 4 h, that is, the γ form had been converted to a noncrystalline solid. After grinding for 1 h at 30°C, about 45% of γ form of IMC was converted to noncrystalline solid, while the product ground for 10 h was transformed to the α form.The Xc of the α form ground for 2 h at 4°C was 0%, that is, the αform had been converted to a noncrystalline solid within 2 h at 4°C. The Xc of the α form ground at 30°C decreased with increasing grinding time and the value after 10 h was about 60%.The solubility in distilled water at 35°C of the γ form ground for 10 h at 4°C was about 60% larger than that of the intact γ form. The solubilities of the γ form gournd for 10 h at 30°C, the α form gound for 10 h at 4°C and the α form gound for 10 h at 30°C were all the same, 0.94 mg/100 ml, which is equal to that of the α form at 35°C.