星点设计-效应面法优化盐酸溴己新吸入粉雾剂的处方  

Formula Optimization of Bromhexine Hydrochloride Dry Powder Inhalations by Central Composite Designresponse Surface Methodology

作　　者：李银科 杨晓松 周子豪 史琼枝 陈晨 廖翔茹 陈鹰 谢向阳 Li Yinke;Yang Xiaosong;Zhou Zihao;Shi Qiongzhi;Chen Chen;Liao Xiangru;Chen Ying;Xie Xiangyang(Department of Pharmacy, Wuhan General Hospital of PEA, Wuhan 430070, Chin)

机构地区：[1]解放军武汉总医院药剂科,武汉430070

出　　处：《中国药师》2018年第6期1010-1015,共6页China Pharmacist

摘　　要：目的:优化盐酸溴己新吸入粉雾剂的处方。方法:采用冷冻干燥-气流粉碎法制备盐酸溴己新吸入粉雾剂,通过星点设计考察甘露醇(X_1),亮氨酸(X_2)和泊洛沙姆188(X_3)在辅料中的用量对盐酸溴己新吸入粉雾剂的休止角(Y_1)、细微粒子剂量(Y_2)和空气动力学粒径(Y_3)的影响。根据最佳数学模型绘制效应面,通过重叠等高线图确定最优处方。结果:影响因素和考察指标之间存在定量关系,优化处方为甘露醇:亮氨酸:泊洛沙姆188在处方中的比例为2.4∶2.22∶0.05。较优处方的各指标实测值与预测值较接近。结论:采用星点设计-效应面法完成了盐酸溴己新吸入粉雾剂的多目标同步优化。Objective： To optimize the formula of bromhexine hydrochloride dry powder inhalations（ BH DPIs）. Methods： BH DPIs were prepared by freezing-drying combined with an air-jet milling method. Three factors,including the weights of mannitol（ X1）,leucine（ X2） and poloxamer 188（ X3） in the formula were known to be associated with the quality of BH DPIs. A central composite design was used to investigate the effects of the three factors on the response angle（ Y1）,fine particle fraction（ FPF,Y3） and aerodynamic diameter（ Y4）. Response surface and overlay contour plot were delineated according to the best-fit mathematic models. Optimum formula was selected by overlay contour plot. Results： The quantitative relationships between the three factors and the three responses were obtained. The optimal formula was mannitol ﹕ leucine ﹕ poloxamer 188（ 2. 4 ∶2. 22 ∶0. 05） in the excipients. The predicted and observed values of the optimum formula were similar. Conclusion： The multi-objective simultaneous optimization of the formula of BH DPIs is achieved by central composite design-response surface methodology.

关 键 词：盐酸溴己新 吸入粉雾剂 星点设计-效应面法 细微粒子剂量 处方筛选 

分 类 号：R944.7[医药卫生—药剂学]