高速剪切湿法制粒工艺制备氯沙坦钾片

Studyon high shear wet granulation process for losartan potassium tablets

目的通过优化高速剪切湿法制粒工艺参数制备氯沙坦钾片。方法采用高速剪切湿法制粒工艺制备氯沙坦钾片,通过对制备工艺参数优化:搅拌桨转速(X_1,r·min^(-1))、加水量(X_2,%)和制粒时间(X_3,s)为考察对象,以颗粒粒径大小(D50,Y_1,μm)、片剂硬度(Y_2,N)、15min药物溶出度(Y_3,%)为评价指标,利用Box-Behnken效应面法优化高速剪切湿法制粒工艺参数。结果方差分析结果显示:搅拌桨转速、加水量和制粒时间对颗粒粒径影响较显著(P<0.05);加水量、制粒时间对片剂的硬度影响较显著(P<0.05);加水量、制粒时间对药物的溶出度影响较显著(P<0.05)。结论通过Box-Behnken实验设计法优化高速剪切湿法制粒工艺,可以提高工艺过程的稳健性和灵活性。

Objective To prepare losartan potassium tablets by optimizing high shear wet granulation process parameters. Methods Using high shear wet granulation process to prepare nanosuspensions. The process variables were optimized by box behnken design（BBD） of response surface methodology（RSM） of impeller speed, water amount and wet massing time as independent variables and particle size distribution, hardness and dissolusion as dependent variables. Results ANOVA showed that the impeller speed, water amount and wet massing time had the largest impact on the granule characteristics（ P 〈0.05 ） ,the water amount and wet massing time had the largest impact on the hardness of tablets （ P 〈 0.05 ）, and the water amount and wet massing time had the largest impact on the dissolution of tablets （ P 〈 0.05 ）. Conclusions Box-Behnken design-response surface methodology was suitable for optimizing the high shear wet granulation process parameters, and could improve the robustness and flexibility of the process.