反溶剂沉淀法制备阿托伐他汀钙微粉

采用反溶剂沉淀法制备阿托伐他汀钙微粉，考察了表面活性剂类型、药物溶液浓度、体系温度和干燥方法对颗粒形貌和大小的影响，得到了适宜的微粉化条件。实验分别利用扫描电镜（SEM）、X射线衍射（XRD）、红外光谱分析（FT-IR）和比表面积（BET）等分析方法对原料及产品的性质进行了表征。研究结果表明：表面活性剂甲基纤维素（MC₂₀）可以有效地控制颗粒形貌;改变溶液浓度及体系温度可以调整颗粒大小;混悬液经喷雾干燥得到的干粉是粒度分布均匀的团粒状类球形颗粒，粒径约为1 μm。微粉化产品为无定形，比表面积高于原料药。此外，还探讨了团粒状类球形颗粒的形成机理。

Preparation of microsized atorvastatin calcium by antisolvent precipitation

The microsized atorvastatin calcium was prepared via the antisolvent precipitation process.The effects of the type of surfactants，drug concentration，precipitation temperature and drying method on particle morphology and particle size were investigated，and the optimum conditions were obtained.The as-prepared microsized atorvastatin calcium and the raw atorvastatin calcium were well characterized by scanning electron microscopy（SEM），powder X-ray diffraction（XRD），Fourier transform infrared spectrometry（FT-IR）and surface area analyzer.The results indicated that methyl cellulose（MC₂₀）was a suitable surfactant to control the particle morphology of atorvastatin calcium.Adjusting drug concentration and system temperature can easily control the particle size and distribution.The spray dried powder with a mean diameter of about 1 μm had a narrow particle size distribution and showed the morphology of granular aggregates composed of smaller spheres.The microsized atorvastatin calcium powder was amorphous，and the specific surface area of the microsized product was higher than the raw atorvastatin calcium.In addition，the possible formation mechanism of granular aggregates composed of smaller spheres was presented.