盐酸丁卡因醇质体的制备工艺优化  

Optimization of Preparation Technology of Tetracaine Hydrochloride Ethosomes

作　　者：张楠[1] 张丹参[1,2] 景永帅[1] 苏晓梅[2] 张健美 ZHANG Nan;ZHANG Danshen;JING Yongshuai;SU Xiaomei;ZHANG Jianmei(College of Chemistry and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China;Dept.of Pharmacology,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北科技大学化学与制药工程学院,石家庄050018 [2]河北医科大学药理学教研室,石家庄050017

出　　处：《中国药房》2019年第24期3369-3374,共6页China Pharmacy

基　　金：中央2017年中药资源普查项目（No.Z135080000022）;河北省自然科学基金资助项目（No.H2016208058）

摘　　要：目的:建立盐酸丁卡因(TCH)醇质体的含量测定方法,并对其制备工艺进行优化。方法:采用高效液相色谱法测定TCH的含量;采用注入-超声法制备TCH醇质体。以TCH对照品加入量、蛋黄卵磷脂质量浓度、乙醇体积分数为因素,以包封率为指标,在单因素试验基础上采用星点设计-响应面法对工艺进行优化,并对所制醇质体进行表征以及初步稳定性考察。结果:TCH的质量浓度线性范围为10~100μg/mL(r=0.9995);定量限为0.045μg/mL,检测限为0.021μg/mL;精密度、稳定性、重复性试验的RSD均小于2%;加样回收率为97.80%~103.20%(RSD=0.36%,n=9)。最优制备工艺为TCH对照品加入量1 mg,蛋黄卵磷脂质量浓度7 mg/mL,乙醇体积分数33%;在此工艺条件下,平均包封率为64.50%(n=3),与预测值(64.92%)的相对误差为0.64%。TCH醇质体为微有蓝色乳光的澄清液体,其外观为球形,形态圆整、光滑,大小均一,平均粒径为(80.33±2.24)nm,平均电位为(-22.6±1.33)mV。初步稳定性试验结果显示,TCH醇质体在4℃避光且密封的环境中放置10 d稳定性良好。结论:优化所得TCH醇质体的制备工艺稳定、可行;所建含量测定方法操作简便、快捷。OBJECTIVE:To establish a method for determining the content of tetracaine hydrochloride(TCH)ethosomes,and to optimize the preparation technology.METHODS:The content of TCH was determined by HPLC.TCH ethosomes were prepared with injection-ultrasonic method.Using drug-loading amount,egg lecithin concentration and ethanol volume fraction as factor,encapsulation efficiency as index,central composite design-response surface methodology was used to optimize the prescription based on the single factor test.The prepared ethosomes were characterized and the stability was evaluated.RESULTS:The linear range of TCH was 10-100μg/mL(r=0.9995);the limit of quantification was 0.045μg/mL,and detection limit was 0.021μg/mL.RSD of precision,stability and repeatability tests were less than 2%.The recoveries ranged 97.80%-103.20%(RSD=0.36%,n=9).The optimal preparation technology included that the adding amount of TCH control was 1 mg;the concentration of egg lecithin was 7 mg/mL,and ethanol volume fraction was 33%.Under this technology,the average encapsulation efficiency was 64.50%(n=3),the relative error of which from the predicted value(64.92%)was 0.64%.TCH ethosome was a clear blue liquid with a blue opalescence.Its appearance was spherical,its shape was round,smooth,uniform in size;the average particle size was(80.33±2.24)nm,and the average Zeta potential was(-22.6±1.33)mV.TCH ethosome was stable during 10 days under 4℃,sealed and protected from light.CONCLUSIONS:The optimal preparation process is stable and feasible.Established method is simple and rapid.

关 键 词：盐酸丁卡因 醇质体 高效液相色谱法 注入-超声法 星点设计-响应面法 包封率 工艺优化 

分 类 号：R944[医药卫生—药剂学]