利用乳糖载体吸附性改善粉末直压奥氮平片的混合均匀度

Improving the Blending Uniformity of Direct Compressed Olanzapine Tablets by Adsorption Effect of Lactose Carrier

本试验以奥氮平片为模型,探究了乳糖载体的吸附性能与粉末直压工艺制备小剂量、难溶性药物片剂时粉末混合均匀度的相关性。采用混合物料的混合均匀度为评价指标,以单因素法考察了不同规格乳糖载体的形态和用量、微粉化奥氮平粒径、混合方法和时间对乳糖载体吸附奥氮平的影响。结果表明,在采用圆形形貌和粗糙表面的喷雾干燥乳糖且其用量高于67%、微粉化奥氮平粒径d(0.9)≤39μm和混合10 min的条件下即可稳定乳糖载体对奥氮平的吸附,使制备过程中粉末混合均匀度的变异系数<2%。验证试验显示,3批奥氮平片的含量均匀度符合要求(A+2.4S<6)。本研究表明,在采用粉末直压工艺制备奥氮平片时,稳定乳糖载体对奥氮平的吸附可确保制备过程中粉末的混合均匀度。

The correlation between the adsorption of lactose carrier and the powder blending uniformity during the preparation process for low-dose tablets of insoluble drugs by direct compression were explored with olanzapine tablets as the model.The influences of micromorphological features of different grades of lactose carrier,the proportion of lactose carrier in the formulation,the particle size of micronized olanzapine,the mixing method and mixing time on the adsorption of olanzapine by the lactose carrier were investigated by single factor test with powder blending uniformity of the mixture as the index.The results showed that the stable absorption of lactose carrier was achieved when using a ratio of 67%or higher amount of spray-dried lactose carrier with round shapes,micronized olanzapine with d(0.9)no more than 39μm and mixing for 10 min,which made the coefficient of variation of powder blending uniformity lower than 2%.The content uniformity of three batches of validation tablets complied with the requirements(A+2.4S<6).It was concluded that stabilizing the adsorption of olanzapine by lactose carrier could ensure blending uniformity during the preparation of olanzapine tablets by direct compression.