张艺蓉,贺佳,任博,尹虹,王晶,万旭春,赵利刚
ZHANG Yirong,HE Jia,REN Bo,YIN Hong,WANG Jing,WAN Xuchun,ZHAO Ligang

• 1:华北理工大学药学院
• 2:呼和浩特市蒙医中医医院药剂科
• 3:唐山市新型药物制剂与释药技术重点实验室

摘要(Abstract)：

目的 制备丁酸氯维地平静脉亚微乳注射液，以期进行质量评价。方法 采用高压均质法制备丁酸氯维地平亚微乳注射液，并以粒径、包封率为评价指标，通过响应面试验设计优化处方，对乳剂粒径、多分散指数(polydispersity index, PDI)、Zeta电位、pH值、渗透压、载药量、包封率、过氧化值和游离脂肪酸值进行评价，考察其稳定性及溶血率。结果 通过响应面试验设计得到优化处方用量：大豆油为10%、中链甘油三酯(medium chain triglycerides, MCT)为10%、蛋黄卵磷脂为1.2%、泊洛沙姆188为0.3%。根据最优处方制得亚微乳粒径为(238.4±0.5)nm, PDI为0.067±0.019,Zeta电位为(-32.8±0.6)mV,pH为7.21±0.07,渗透压为(296±1)mOsmol·kg~(-1),载药量为(0.50±0.02)g·L~(-1),包封率为(98.96±0.62)%,过氧化值、游离脂肪酸值均符合质量要求。稳定性研究显示亚微乳在(4±2)℃条件下可以稳定保存6个月，溶血试验结果表明其溶血率低于安全阈值。结论 优化制备的丁酸氯维地平亚微乳性质稳定，安全性高，有一定开发前景，有望用于进一步临床前研究。
Objective To develop a submicron emulsion of clevidipine butyrate(CLB)for quality evaluation.Methods The CLB submicron emulsion was prepared by high pressure homogenization methods.The formulation was optimized by response surface methodology using the particle size and encapsulation efficiency as the evaluation indicators.The particle size, polydispersity index(PDI),Zeta potential, pH value, osmotic pressure, entrapment efficiency, drug loading, peroxide value, free fatty acid value and the stability were investigated, respectively.Results The results showed that the optimal formulation was composed of 10%soybean oil, 10%MCT,1.2%egg yolk lecithin and Polosham 188 0.3%.The droplet size, PDI,Zeta potential and pH value of CLB submicron emulsion were(238.4±0.5)nm, 0.067±0.019,(-32.8±0.6)mV and 7.21±0.07.The drug loading, encapsulation efficiency and osmotic pressure were(0.50±0.02)g·L~(-1),(98.96±0.62)%and(296±1)mOsmol·kg~(-1),respectively.The peroxide value and free fatty acid met the quality requirements.The results of stability test showed that the product could maintain stable for 6 months at(4±2)℃ under light-resistant conditions.The hemolysis rate was lower than the safety threshold.Conclusion The CLB submicron emulsion owns stable nature, high safety and have promising values for clinical application.

关键词(KeyWords)： 丁酸氯维地平;亚微乳;响应面试验设计;质量评价;稳定性试验
clevidipine butyrate;submicron emulsion;response surface methodology;quality evaluation;stability test

Abstract:

Keywords:

基金项目(Foundation): 河北省“第三批青年拔尖人才”项目;; 华北理工大学杰出青年基金项目(JQ201713)

作者(Author): 张艺蓉,贺佳,任博,尹虹,王晶,万旭春,赵利刚
ZHANG Yirong,HE Jia,REN Bo,YIN Hong,WANG Jing,WAN Xuchun,ZHAO Ligang

DOI: 10.14066/j.cnki.cn21-1349/r.2021.0825

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