地塞米松棕榈酸酯亚微乳注射液的制备及质量评价  

Preparation and evaluation of dexamethasone palmitate submicron emulsion injection

作　　者：尹虹 张金伟 李翰铭 吴燕 邢佳丽 曹宇佳 赵利刚 YIN Hong;ZHANG Jinwei;LI Hanming;WU Yan;XING Jiali;CAO Yujia;ZHAO Ligang(School of Phamacy,North China University of Science and Technology,Tangshan 063000,China;Tangshan Key Lab.of Novel Preparations and Drug Release Technolog,Tangshan 063000,China)

机构地区：[1]华北理工大学药学院,河北唐山063000 [2]唐山市新型药物制剂与释药技术重点实验室,河北唐山063000

出　　处：《沈阳药科大学学报》2024年第9期1162-1170,共9页Journal of Shenyang Pharmaceutical University

基　　金：河北省“第三批青年拔尖人才”项目(201807)。

摘　　要：目的制备地塞米松棕榈酸酯亚微乳注射液,对其理化特性和安全性进行评价。方法利用高压均质法制备地塞米松棕榈酸酯亚微乳注射液,以粒径和包封率为评价指标,通过响应面法优化处方中油相(大豆油与中链甘油三酸酯质量比1∶1)、蛋黄卵磷脂和泊洛沙姆188(F68)的用量。对优化处方所得亚微乳的粒径、多分散性指数(PDI)、Zeta电位、pH值、载药量、包封率、渗透压、游离脂肪酸及溶血性进行评价,并考察其稳定性和体外释放行为。结果通过响应面设计得优化处方量为大豆油为5%,中链甘油三酸酯为5%,蛋黄卵磷脂为1.2%,F68为0.3%。测得优化处方亚微乳粒径为(188.1±2.5)nm,PDI为0.093±0.025,Zeta电位为(-38.4±0.643)mV,pH值为7.12±0.13,载药量为(3.96±0.05)mg·mL^(-1),包封率为(97.9±0.28)%,渗透压为(294±1)mOsmol·kg^(-1)。游离脂肪酸值符合要求,稳定性试验结果表明,该亚微乳可在(4±2)℃、避光条件下稳定贮存12个月;溶血实验结果中最大溶血率为1.83%;体外释放结果符合一级动力学模型。结论通过响应面法优化所制备的地塞米松棕榈酸酯亚微乳性质稳定、安全性较高,具有一定的缓释效果。Objective To prepare a dexamethasone palmitate(DMP)submicron emulsion injection and to investigate its physicochemical properties and safety.Methods The DMP submicron emulsion was prepared by high pressure homogenization method.The formulation amounts of oil phase(LCT:MCT=1∶1),egg yolk lecithin and poloxamer 188 were optimized by the response surface methodology with the particle size and entrapment efficiency as the indicators.And then the particle size,polydispersity index(PDI),Zeta potential,pH value,drug loading,entrapment efficiency,osmotic pressure,free fatty acid value,hemolysis,stability and in vitro release were evaluated respectively.Results The results showed that the optimal formulation should be composed of 5%soybean oil,5%MCT,1.2%egg yolk lecithin and 0.3%Poloxamer 188.The mean particle size,PDI,Zeta potential and pH value of DMP submicron emulsion were(188.1±2.5)nm,0.093±0.025,(-38.4±0.643)mV and 7.12±0.13.The drug loading,encapsulation efficiency and osmotic pressure were(3.96±0.05)mg·mL^(-1),(97.91±0.28)%and(294±1)mOsmol·kg^(-1),respectively.The free fatty acid value meets the quality requirements.The results of stability test showed that the product could maintain stable for 12 months at(4±2)℃under light-resistant conditions.The maximum hemolysis rate was 1.83%.The release result of DMP submicron emulsion was followed the first release equations.Conclusion The DMP submicron emulsion prepared in this study is stable,safe and have a sustained release effect.

关 键 词：地塞米松棕榈酸酯 亚微乳 响应面法 质量评价 稳定性 

分 类 号：R94[医药卫生—药剂学]