摘要
目的对左旋硫酸沙丁胺醇、盐酸氨溴索复方干粉吸入剂的载体进行筛选及其制备工艺优化。方法将2种药物、不同辅料分别经实验型喷雾干燥仪制备药物、载体颗粒,测定粉末的粉体学参数并进行比较,包括休止角、含水量、密度、沉积率和排空率等,确定载体辅料。并应用Box-Behnken设计法优化制备工艺参数。结果以乳糖-高分支环糊精为复合载体时,其粉体学性质较好,其休止角为39.69°,堆密度0.37 g·m L^(-1),振实密度0.66 g·m L^(-1),排空率93.12%,含水量0.10%,模拟肺部沉积率14.63%。优化后样品浓度、进风温度、喷嘴直径参数,其值分别为50 mg·m L^(-1)、110℃、1 mm,制得载体粒径为30.33μm。结论乳糖-高分支环糊精复合物可作为左旋硫酸沙丁胺醇、盐酸氨溴索复方干粉吸入剂的载体,经喷雾干燥后其体外粉体参数验证符合要求。
OBJECTIVE To select excipients and optimize preparation for the ambroxol hydrochloride/levosalbutamol sulfate dry powder inhalation. METHODS Drug and different exeipients in the same ratio were prepared by spray drying to obtain a certain particle size as drug particles or carriers for dry powder inhalation, respectively. Study and compare the parameters of powders of the dry powder inhaler, such as the angle of repose, moisture content, and emptying rate, etc, to screen the exeipient of the vectors. Afterward, Box-Behnken design method was adopted to optimize of preparation parameters. RESULTS When lactose-high branched cyclo- dextrin compounds were used as composite carriers, their powder properties meet the requirements of dry powder inhaler, such as the repose angle was 39. 69 degrees, the bulk density was 0. 37 g· mL - 1, the tap density was 0. 66 g · mL- 1, the evacuation rate of drugcarrier powders in capsules was 93.12% , and the water content was 0. 10% and the simulated lung deposition rate was 14. 63%. The preparation parameters, such as sample concentration, inlet air temperature, nozzle diameter parameters, theirs values were 50 mg · mL- 1 , 110℃, 1 mm, respectively, were opmized by Box-Behnken design method, which could obtain the carrier particle size of 30. 33 p,m. CONCLUSION Lactose-high branched cyclodextrin complexes can be used as carrier for levosalbutmnol sulfate-ambroxol hydrochloride compound dry powder inhaler, which could meet the requirements of dry powder inhaler by spray-drying preparation method.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2017年第23期2104-2111,共8页
Chinese Pharmaceutical Journal
基金
河北省卫生厅科研基金项目资助(20120217)
关键词
左旋硫酸沙丁胺醇
盐酸氨溴索
粉雾吸入剂
喷雾干燥法
制备
levosalbutamol sulfate
ambroxol hydrochloride
dry powder inhaler
spray-drying method
preparation
