Effect of Environmental Temperature on Polymorphic Solid-State Transformation of Indomethacin during Grinding

概要

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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℃ ant at 30±0.5℃, and the degree of crystallinity (X_c) of the ground products was measured by the X-ray diffractional internal standard method.The X_c of the γ form ground at 4℃ 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℃, 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 X_c of the α form ground for 2 h at 4℃ was 0%, that is, the αform had been converted to a noncrystalline solid within 2 h at 4℃. The X_c of the α form ground at 30℃ decreased with increasing grinding time and the value after 10 h was about 60%.The solubility in distilled water at 35℃ of the γ form ground for 10 h at 4℃ was about 60% larger than that of the intact γ form. The solubilities of the γ form gournd for 10 h at 30℃, the α form gound for 10 h at 4℃ and the α form gound for 10 h at 30℃ were all the same, 0.94 mg/100 ml, which is equal to that of the α form at 35℃.
社団法人日本薬学会の論文
1986-04-25