目的: 测定定量型吸入气雾剂参比制剂和受试制剂各3批的喷雾模式和喷雾形态、递送剂量,判断参比制剂和受试制剂体外雾化形态和剂量的等效性。方法: 采用激光成像系统测定硫酸沙丁胺醇吸入气雾剂的喷雾模式和喷雾形态,以喷射角度和喷射宽度作为喷雾形态的评价参数,以椭圆比和喷射面积作为喷雾模式的评价参数,对结果进行体外群体等效性分析。结合递送剂量测定结果,判断参比制剂和受试制剂的体外等效性。结果: 参比制剂和受试制剂喷射角度几何平均值的比值分别为98.2%(3 cm)、97.1%(6 cm),喷射宽度几何平均值的比值分别为97.4%(3 cm)、98.4%(6 cm),对3 cm和6 cm处的椭圆比、喷射面积、喷射角度、喷射宽度分别进行群体等效分析,得到各参数的95%置信区间的上限值,椭圆比均为-0.02(3 cm和6 cm),喷射面积分别为-0.01(3 cm)和-0.02(6 cm),喷射角度均为-0.02(3 cm和6 cm),喷射宽度均为-0.02(3 cm和6 cm)。参比制剂和受试制剂的递送剂量相差较大,受试制剂的递送剂量均一性较好。结论: 参比制剂和受试制剂在喷雾模式和喷雾形态项目评价为等效,但递送剂量均一性经非参数检验判定为不等效。本文为仿制制剂的处方、工艺和雾化装置筛选提供依据,为仿制制剂的体外雾化形态的等效性评价提供参考,为吸入制剂的仿制药品研发和体外评价提供思路。
Objective: To determine spray pattern, plume geometry and delivered dose of the reference products and the tested products of salbutamol sulfate inhalation aerosol, and judge the atomization characteristic equivalence in vitro of the reference and test products. Methods: Spray pattern and plume geometry of salbutamol sulfate inhalation aerosol were determined by Spray VIEW. Plume geometry was evaluated with plume angle and plume width. Spray pattern was evaluated with spray area and ovality. The results were analyzed by population bioequivalence (PBE).Combined with the results of delivered dose, equivalence in vitro of the reference products and the tested products was further judged. Results: The ratios of the average of the geometric mean of plume angle of the reference and the test products were 98.2%(3 cm), 97.1%(6 cm), respectively, and the average of the geometric mean of plume width were 97.4%(3 cm) and 98.4%(6 cm), respectively. The spray area, ovality, plume angle and plume width at 3 cm and 6 cm were analyzed by PBE. The upper limits of the 95% confidence interval of ovality were -0.02(3 cm) and -0.02(6 cm), respectively. The upper limits of the 95% confidence interval of spray area were -0.01 (3 cm) and -0.02 (6 cm), respectively. The upper limits of the 95% confidence interval of plume angle were -0.02(3 cm) and-0.02(6 cm), respectively. The upper limits of the 95% confidence interval of plume width were-0.02(3 cm) and -0.02(6 cm), respectively. The delivered dose of the reference products and the test products were different, and the delivered dose of the test products was more uniform. Conclusion: The reference and the test products are equivalent in spray pattern and plume geometry, but the uniformity of delivery dose is non-equivalent by nonparametric test. It provides choices for the formulation, process and atomization device screening of generic products, offers the evaluation method of atomization characteristic in vitro, and provides ideas for the development and evaluation in vitro of generic products.
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