共研磨法制备吸入用丹酚酸-丹参酮复合微粉及其表征  

Preparation and characterization of salvianolic acids-tanshinones composite powder for inhalation via co-micronized method

作　　者：翟文文[1] 戴俊东[1] 刘乐环 黄瑞雪[1] 黎翊君 茅玉炜 蒋俏丽 

机构地区：[1]北京中医药大学中药学院,北京100102

出　　处：《中国中药杂志》2016年第4期659-665,共7页China Journal of Chinese Materia Medica

基　　金：北京中医药大学自主选题项目(2015-JYB-XS108)

摘　　要：建立了一种将丹参中的脂溶性和水溶性有效成分共微粉化的方法,制备得到了适用于肺部吸入给药的丹酚酸-丹参酮复合微粉。以湿法球磨粉碎为制备方法,复合微粉1~5μm体积分数为评价指标,采用中心组合实验设计（central composite design,CCD）-效应面法进行工艺优化。通过扫描电镜、激光粒度分布仪、X-射线衍射分析仪等对复合微粉进行质量评价,并测定其流动性和引湿性。结果显示最优制备工艺条件下得到的丹酚酸-丹参酮复合微粉粒径分布均一,D50为2.33μm,1~5μm体积分数为80.82%,休止角为（50.60±1.13）°,临界相对湿度约为77%。共微粉化使药物微粒的粒径显著减小,药物的无定形物稍有增加,对粉体的流动性、吸湿性无显著影响。该研究表明湿法球磨可用于性质差异大的多种成分的共微粉化,制备得到适于吸入的丹酚酸-丹参酮复合微粉,为进一步吸入粉雾剂的制备提供基础。Salvianolic acids and tanshinones are main hydrophilic and lipophilic extracts from Salvia Miltiorrhiza with significant antipulmonary 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. 33μm. The volume fraction of particle size in 1-5 μm was 80. 82%. The repose angle was（ 50. 60 ± 1. 13）o,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.

关 键 词：丹参总酚酸 总丹参酮 湿法球磨粉碎 中心组合实验设计 吸入粉雾剂 

分 类 号：R283[医药卫生—中药学]