阿利维A酸原料药的微粉化工艺研究

摘要

目的:筛选阿利维A酸原料药的微粉化工艺.方法:以原料药粉碎后的粒径分布特征值[d(0.9)]和杂质A含量为指标,筛选阿利维A酸原料药的粉碎方式(万能粉碎机、球磨机、气流粉碎机)、粉碎气源(压缩空气、高压氮气)、粉碎压力(0.2、0.4、0.6 MPa),并进行验证试验.结果:最优工艺为采用气流粉碎机以高压氮气作为气源在0.4 MPa下粉碎;验证试验中3批原料药粉碎后的粒径分别为8.57、8.55、8.54 μm(均小于10 μm,RSD=0.15%,n=3),杂质A的含量与未粉碎前比较未见增加(均为0.07%).结论:筛选的阿利维A酸原料药的微粉化工艺操作可行、质量稳定.%OBJECTIVE:To screen the optimal micronization technology of Alitretinoin crude drug. METHODS:Using characteristic value of particle size distribution [d(0.9)] and the content of impurity A of crude drug after crushed as indexes, crushing method(universal pulverizer,ball crusher,airslide disintegrating mill),crushing gas source(compressed air,high pressure nitrogen)and crushing pressure(0.2,0.4,0.6 MPa)of Alitretinoin crude drug were screened,and validation test was also conducted. RESULTS:The optimal technology was as follows as airslide disintegrating mill,high pressure nitrogen as gas source,at 0.4 MPa.In validation test,particle sizes for 3 batches of crude drug after crushed were 8.57,8.55,8.54 μm(<10 μm, RSD=0.15%,n=3). The content of impurity A was not increased compared with before crushed(0.07%). CONCLUSIONS:Screened micronization technology of Alitretinoin crude drug is feasible and stable in quality.