Xiong Xinnuo, Xu Kailin, Li Shanshan, Tang Peixiao, Xiao Ying, Li Hui
a College of Chemical Engineering, Sichuan University , Chengdu , China.
Drug Dev Ind Pharm. 2017 Feb;43(2):283-292. doi: 10.1080/03639045.2016.1239627. Epub 2016 Oct 6.
Solid-state amorphization of crystalline rebamipide (RBM) was realized by ball milling and spray drying. The amorphous content of samples milled for various time was quantified using X-ray powder diffraction. Crystalline RBM and three amorphous RBM obtained by milling and spray drying were characterized by morphological analysis, X-ray diffraction, thermal analysis and vibrational spectroscopy. The crystal structure of RBM was first determined by single-crystal X-ray diffraction. In addition, the solubility and dissolution rate of the RBM samples were investigated in different media. Results indicated that the solubility and the dissolution rates of spray-dried RBM-PVP in different media were highly improved compared with crystalline RBM. The physical stabilities of the three amorphous RBM were systematically investigated, and the stability orders under different storage temperatures and levels of relative humidity (RH) were both as follows: spray dried RBM < milled RBM < spray dried RBM-PVP. A direct glass-to-crystal transformation was induced under high RH, and the transformation rate rose with increasing RH. However, amorphous RBM could stay stable at RH levels lower than 57.6% (25 °C).
通过球磨和喷雾干燥实现了结晶型瑞巴派特（RBM）的固态非晶化。使用X射线粉末衍射对研磨不同时间的样品的非晶含量进行了定量。通过形态分析、X射线衍射、热分析和振动光谱对通过研磨和喷雾干燥获得的结晶型RBM和三种非晶型RBM进行了表征。首先通过单晶X射线衍射确定了RBM的晶体结构。此外，还研究了RBM样品在不同介质中的溶解度和溶解速率。结果表明，与结晶型RBM相比，喷雾干燥的RBM-PVP在不同介质中的溶解度和溶解速率有了显著提高。系统研究了三种非晶型RBM的物理稳定性，不同储存温度和相对湿度（RH）水平下的稳定性顺序均为：喷雾干燥的RBM＜研磨的RBM＜喷雾干燥的RBM-PVP。在高RH条件下诱导了直接的玻璃态到晶态的转变，且转变速率随RH的增加而升高。然而，非晶型RBM在低于57.6%（25℃）的RH水平下可以保持稳定。
