目的:建立激光衍射法测定盐酸溴己新原料药的粒度及分布, 探讨原料药粒度对药物制剂体外溶出的影响。方法:Malvern Mastersizer 3000 激光粒度仪, AERO S 干法进样器; 背景测量时间10 s, 样品测量时间15 s; 遮光度范围为0.50%~5%; 颗粒折射率1.626, 吸收率0.1; 分析模型为通用的细的干粉模型; 样品分散气压为350 kPa; 进样速度为40%; 料斗间隙为2.0 mm; 样品量为200 mg。结果:激光衍射法可准确测定盐酸溴己新原料药粒度分布, 方法精密度和样品测定值RSD 均小于5%。4批自制样品粒径分布值d0.9 分别为30.05、40.60、48.60 和82.20 μm, 且原料药的粒径越大, 制成颗粒剂的溶出速度越慢。结论:本方法适合盐酸溴己新原料药的粒度分布测定, 且盐酸溴己新原料药的粒度分布对其颗粒剂的溶出有显著影响, 在药物制剂生产过程中进行粒度控制至关重要。
王越, 吴松, 薛丹, 张坤, 邵会会, 徐卫国, 张对良, 张嵩, 杨庆云
. 激光衍射法测定盐酸溴己新粒度分布的方法学研究*[J]. 药物分析杂志, 2021
, 41(8)
: 1448
-1453
.
DOI: 10.16155/j.0254-1793.2021.08.20
Objective：To establish a laser light diffraction method for determination of the particle size and particle size distribution of bromhexine hydrochloride, and to explore the effect of the particle size of active pharmaceutical ingredient (API) on the dissolution in vitro. Methods：The Malvern Mastersizer 3000 laser particle size analyzer with AERO S dry sampler was used. The determination conditions were as follows：background measurement time：10 s, sample measurement time：15 s, obscuration：0.50%-5%, particle RI∶1.626, particle AI∶0.1, analysis model：general, fine dry powder model, pressure：350 kPa, sampling velocity：40%, hopper gap：2.0 mm, sample weight：200 mg. Results：The laser diffraction method could be used to determine the particle size of bromhexine hydrochloride. The relative standard deviation values (RSD%) of methodology validation and sample measurement were less than 5%. The particle size distribution values of 4 batches of self-made samples were 30.05, 40.60, 48.60 and 82.20 μm, respectively. The larger the particle size of the API, the slower the dissolution rate of the granules. Conclusion：The method is suitable for the particle size and its distribution determination of bromhexine hydrochloride. And the particle size distribution of bromhexine hydrochloride has significant influence on the release of granules, therefore it is very important to control the particle size in the production process of pharmaceutical preparation.
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