前列地尔注射液配伍试验中乳粒稳定性的探讨  

Stability measurement of alprostadil injections' globule in a compatible experiment

作　　者：潘伟祥[1] 刘洁[1] 何军[1] 杨亚妮[1] 卞玮[1] 张薇薇[1] 

机构地区：[1]中国医药工业研究总院,药物制剂国家工程研究中心,上海200437

出　　处：《中国新药杂志》2013年第18期2201-2205,2214,共6页Chinese Journal of New Drugs

基　　金：上海市科委2012年度"科技创新行动计划"纳米科技专项:前列地尔固态纳米乳工程化制备技术研究及安全性评价(12nm0502500)

摘　　要：目的:以平均粒径和大粒子比例(≥5μm)作为指标,考察2种市售前列地尔注射液的配伍试验中乳粒的物理稳定性。方法:参考国家标准和美国药典(United States Pharmacopoeia,USP)的要求,考察样品不稀释,或与生理盐水/5%葡萄糖注射液稀释混合后,室温放置8 h内平均粒径和粒径分布的变化。结果:A和B两厂家样品在8 h内平均粒径与90%累积粒径均符合国家标准。A厂家样品不经稀释和用生理盐水稀释时,PFAT5(percentage of fat globules>5μm,表示体积径>5μm的乳粒体积之和与分散相总体积的百分比)8 h内符合USP限度(PFAT5≤0.05%);用5%葡萄糖注射液稀释后,4 h内PFAT5符合USP限度要求,4 h后PFAT5超出USP限度。B厂家样品在3组实验中PFAT5均超出USP限度。结论:动态光散射法(dynamic light scattering,DLS)法适用于测量脂肪乳注射液平均粒径,而光消减-单粒子光学传感(light extinction-single partical optical sensing,LE/SPOS)法是评价大粒子粒径分布更为有效的方法,因此建议采用2种方法相结合,从而对乳剂的粒径进行更全面科学的质量控制(包括平均粒径和大粒子)。Objective： To determine the physical stability of two commercial alprostadil injections in a com- patible experiment with the mean particle size and globule size distribution （≥ 5 μm） as indicators. Methods： Samples were either mixed with normal saline, or 5% glucose injection, or in a third way without dilution. Then, National and USP standards were referred to measure mean droplet size and globule size distribution of the diluted injection within 8 h at room temperature. Results： The mean droplet size and 90% cumulative particle size of both commercial alprostadil injections within 8 h fitted National standard. Sample A, without dilution or mixed with nor- mal saline, met the standard of USP （PFAT5 ≤0.05% ） within 8 h. When it was diluted in 5% glucose injection, the PFAT5 was greater than 0.05% after 4 h, which did not meet the requirement of USP. For sample B, the PFAT5 of all three dilution injections were not within the limit of 0. 05% , and did not meet the standard of USP. Conclusion： The dynamic light scattering （DLS） is suitable for measuring mean droplet size of the lipid injectable emulsions; while light extinction-single particle optical sensing （LE/SPOS） is more appropriate and effective for e-valuating the distribution of large globule droplet. Therefore, a combination of 2 methods is considered to be scien- tifically more comprehensive （including mean droplet size and large globule distribution） for quality control.

关 键 词：前列地尔 脂肪乳注射液 平均粒径 粒径分布 

分 类 号：R943.3[医药卫生—药剂学]