Zhai Wen-Wen, Dai Jun-Dong, Liu Le-Huan, Huang Rui-Xue, Li Yi-Jun, Mao Yu-Wei, Jiang Qiao-Li
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Zhongguo Zhong Yao Za Zhi. 2016 Feb;41(4):659-665. doi: 10.4268/cjcmm20160419.
Salvianolic acids and tanshinones are main hydrophilic and lipophilic extracts from Salvia Miltiorrhiza with significant anti-pulmonary fibrosis effects. The aim of this study was to prepare a co-micronized salvianolic acids-tanshinones composite powder for inhalation using a planetary ball mill. The micronization process parameters were optimized by central composite design (CCD) and response surface methodology (RSM). Treatment time, rotation speed and the ball/sample weight ratio were selected as the independent variables, and the volume fraction of particle size in 1-5 μm was taken as the dependent variable. The powder properties were evaluated by scanning electron microscopy (SEM), laser diffraction and X-ray powder diffraction (XRPD). The powder flow and hygroscopicity were determined with repose angle, compressibility index and critical relative humidity(CRH). According to the results, the salvianolic acids-tanshinones composite powder produced in optimal conditions had a narrow and unimodal particle size distribution and a smaller D₅₀ of 2.33 μm. The volume fraction of particle size in 1-5 μm was 80.82%. The repose angle was (50.60±1.13) °, and the critical relative humidity is about 77%. After being micronized, the particle size significantly reduced, and the number of amorphous substances slightly increased, with no significant changes in powder flow and hygroscopicity. These findings indicate that the grinding method with a planetary ball mill can be used to co-micronize various components with different properties and prepare composite drug powders for dry powder inhalation.
丹参酚酸和丹参酮是丹参主要的亲水性和脂溶性提取物，具有显著的抗肺纤维化作用。本研究旨在采用行星球磨机制备用于吸入的丹参酚酸 - 丹参酮共微粉化复合粉末。通过中心复合设计（CCD）和响应面方法（RSM）对微粉化工艺参数进行优化。选择处理时间、转速和球/样品重量比作为自变量，将粒径在1 - 5μm的颗粒体积分数作为因变量。通过扫描电子显微镜（SEM）、激光衍射和X射线粉末衍射（XRPD）对粉末特性进行评估。用休止角、压缩性指数和临界相对湿度（CRH）测定粉末流动性和吸湿性。结果表明，在最佳条件下制备的丹参酚酸 - 丹参酮复合粉末具有窄且单峰的粒径分布，D₅₀较小，为2.33μm。粒径在1 - 5μm的颗粒体积分数为80.82%。休止角为（50.60±1.13）°，临界相对湿度约为77%。微粉化后，粒径显著减小，无定形物质数量略有增加，粉末流动性和吸湿性无显著变化。这些研究结果表明，行星球磨机研磨方法可用于将具有不同性质的各种成分共微粉化，制备用于干粉吸入的复合药物粉末。
