塞来昔布自微乳的制备及体外溶出研究  

Preparation of Celecoxib Self-microemulsion and Evaluation on Its In Vitro Dissolution

作　　者：杨雪华 毛楷凡 刘正平 李大伟 张岱州 YANG Xue-hua;MAO Kai-fan;LIU Zheng-ping;LI Da-wei;ZHANG Dai-zhou(Shandong Engineering Research Center of Novel Sustained and Controlled Release Formulations and Targeted Drug Delivery Systems,Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China;NMPA Key Laboratory for Technology Research and Evaluation of Drug Products,Jinan 250101,China;Shandong Key Laboratory of Mucosal and Skin Administration Technology,Shandong Freda Pharmaceutical Group Co.,Ltd.,Jinan 250101,China)

机构地区：[1]山东省药学科学院,新型缓控释制剂与药物靶向递送系统山东省工程研究中心,山东济南250101 [2]国家药监局药物制剂技术研究与评价重点实验室,山东济南250101 [3]山东福瑞达医药集团有限公司,山东省黏膜与皮肤给药技术重点实验室,山东济南250101

出　　处：《食品与药品》2023年第4期302-307,共6页Food and Drug

基　　金：山东省重点研发计划(重大科技创新工程)资助项目(编号:2021CXGC010515)。

摘　　要：目的 将塞来昔布(CXB)制备成自微乳药物递送系统(SMEDDS),以提高CXB的溶解度和生物利用度。方法 通过伪三元相图的绘制和单纯形网格法优化筛选出CXB-SMEDDS的最佳处方,然后对制备的CXB-SMEDDS进行质量评价和体外溶出研究。结果 优化后的CXB-SMEDDS处方组成为中链甘油三酯(MCT)10%、聚氧乙烯35蓖麻油(ELP35)60%、丙三醇30%,其在室温下为无色透明溶液,载药量为标示量的(101.42±0.29)%,包封率为(98.05±0.18)%,乳化时间为(8.42±0.63)s,乳化后能形成略泛蓝光的乳液,乳液在微观上呈圆球形结构,大小较为均一,并通过粒度仪测得其粒径为(16.21±0.72)nm,电位为(-15.8±1.2)mV,聚合物多分散指数(PDI)为0.072±0.011。体外溶出试验结果显示,与CXB原料药相比,CXB-SMEDDS的溶出度大大提高。结论 CXB-SMEDDS制备工艺简单,质量稳定,能显著提高CXB的溶解度和体外溶出度。Objective To prepare self-microemulsifying drug delivery system(SMEDDS)of celecoxib(CXB)and increase its solubility and bioavailability.Methods The prescription was optimized by pseudo-ternary phase diagram and simplex lattice design method.And the quality and in vitro dissolution of the prepared CXB-SMEDDS were evaluated.Results The optimal prescription of CXB-SMEDDS was as follows:MCT 10%,ELP3560%,glycerol 30%.Before self-emulsification,CXB-SMEDDS was a colorless and transparent solution at room temperature.The drug loading was(101.42±0.29)%of the labeled amount,the encapsulation efficiency was(98.05±0.18)%,and the emulsification time was(8.42±0.63)s.After self-emulsification,CXB-SMEDDS could form a clear and slightly blue-colored emulsion,and the emulsion had a spherical structure with relatively uniform size on the microscopic scale.In addition,the particle size,Zeta potential and PDI measured by particle size analyzer were (16.21±0.72) nm, (-15.8±1.2) mV, and 0.072±0.011, respectively. The results of in vitro dissolution study revealed that the dissolution rate of CXB-SMEDDS was greatly improved compared with that of CXB API. Conclusion The optimized CXB-SMEDDS possesses advantages of easy preparation process and stable quality and can significantly improve the solubility and in vitro dissolution.

关 键 词：塞来昔布 自微乳 三元相图 单纯形网格法 体外溶出 

分 类 号：R943[医药卫生—药剂学]