咪唑安定微乳滴鼻液的制备及质量控制  

Preparation and quality control of midazolam microemulsion nasal drops

作　　者：田睿[1] 甘勇军[1] 徐颖[2] 

机构地区：[1]重庆医科大学生命科学研究院,重庆400016 [2]重庆医科大学附属儿童医院麻醉科儿童发育疾病研究省部共建教育部重点实验室,重庆400014

出　　处：《第三军医大学学报》2011年第1期82-85,共4页Journal of Third Military Medical University

基　　金：重庆市卫生局项目(072161)~~

摘　　要：目的研究水包油(O/W)型咪唑安定微乳滴鼻液的制备工艺和质量检测方法。方法考察咪唑安定在不同油、表面活性剂、助表面活性剂中的平衡溶解度,选择平衡溶解度较大的试剂通过滴定法制备伪三元相图,根据相图优选处方,采用HPLC法测定咪唑安定在微乳中的含量。结果咪唑安定微乳的优选处方为油酸乙酯:吐温80:聚乙二醇-400:水体系,表面活性剂与助表面活性剂的比为Km=2∶1,粒径为(37.93±8.34)nm。咪唑安定在10～90μg/m l范围内线性关系良好(r=0.999 9),低、中、高3个浓度的回收率(n=3)分别为99.39%、99.46%和99.36%,RSD分别为0.57%、0.67%和0.85%。结论该处方制备的咪唑安定微乳粒径小,稳定性好,制备工艺简便,质量控制方法准确可靠。Objective To study the preparation process and quality control method of O/W midazolam microemulsion nasal drops.Methods The equilibrium solubility of midazolam in different systems of oils,surfactants and cosurfactants were tested.A pseudo-ternary phase diagram was constructed through titration on those reagents with high midazolam equilibrium solubility,and an optimum microemulsion formulation was chosen based on the phase diagram.The content of midazolam in the microemulsion was determined by HPLC.Results The optimum microemulsion formulation was composed of ethyl oleate,Tween-80,PEG-400 and water.The weight ratio of surfactant to cosurfactant was 2∶1.The average particle size was 37.93±8.34 nm.Midazolam showed good linearity（r=0.999 9） in the range of 10-90 μg/ml.The average recoveries of high（60 μg/ml）,middle（50 μg/ml） and low（40 μg/ml） midazolam concentrations（n=3 for each concentration） were 99.39%,99.46% and 99.36% with RSD of 0.57%,0.67% and 0.85%,respectively.Conclusion The prepared midazolam microemulsion has advantages of small particle sizes,high stability and simple preparation process.The quality control method is accurate and reliable.

关 键 词：咪唑安定 微乳 伪三元相图 高效液相色谱 

分 类 号：R944.1[医药卫生—药剂学] R954[医药卫生—药学]