水飞蓟宾-熊去氧胆酸共无定形物胶囊的处方设计

Formulation design of silybin-ursodeoxycholic acid co-amorphous capsule

目的粉末直接灌装胶囊的方法制备摩尔比为1∶1的水飞蓟宾-熊去氧胆酸共无定形物(SUE0101)胶囊。方法采用单因素实验对填充剂和助流剂的种类和含量进行初步的筛选。以胶囊的体外溶出度和胶囊内容物的休止角为指标通过响应曲面法中的中心复合设计优化胶囊填充剂和助流剂的精确含量,填充剂和助流剂的含质量分数取值为20%~40%和0.5%~1.5%设计实验,零点重复两次,筛选出最佳用量,同样的指标筛选制备胶囊的最佳工艺。按照最优处方重复三次验证水飞蓟宾-熊去氧胆酸胶囊处方工艺的稳定性和一致性。结果得到最佳工艺和最优处方:乳糖含量质量分数为40%,气相二氧化硅200含量质量分数为1.25%。将最优处方的最佳工艺重复三次验证,证明胶囊的处方工艺科学、稳定、可行。结论成功制备出工艺稳定、安全可行的水飞蓟宾-熊去氧胆酸共无定形物胶囊。

Objective To prepare capsule by directly filling powder into capsule, the silybinursodeoxycholic acid co-amorphous(SUE0101) powder is used as an intermediate. Methods Through a single-factor experiment, according the in vitro dissolution and the angle of repose of capsule content,the type and content of filler and glidant were preliminary screened. Using the central composite design method of response surface methodology, the experiment was conducted with the filler and glidant ranging from 20% to 40% and 0.5% to 1.5% and was repeated twice at zero. According the in vitro dissolution and the angle of repose of capsule content, the best preparation process was confirmed.Results The best formulation was 40% of lactose and 1.25% of aerosol 200. SUE 0101, lactose, and aerosil200 were passed through an 80-mesh sieve, respectively. SUE0101 and aerosol 200 were added in equal amounts. The mixture was then mixed with lactose added by equal amounts, and the above total mixture was vortexed for 10 min. Silybin-ursodeoxycholic acid co-amorphous capsules were finally prepared. Conclusions The silybin-ursodeoxycholic acid co-amorphous capsule is successfully prepared,and the preparation process of capsule is stable and feasible.