美洛昔康纳米混悬液的制备及质量评价  

Preparation and Quality Evaluation of Meloxicam Nanosuspension

作　　者：毕嘉威 刘金霞 赵钰萌 刘艳华[1,2] BI Jiawei;LIU Jinxia;ZHAO Yumeng;LIU Yanhua(College of Pharmacy,Ningxia Medical University,Yinchuan 750004;Key Lab.of Hui Ethnic Medicine Modernization,Ministry of Education,Ningxia Medical University,Yinchuan 750004)

机构地区：[1]宁夏医科大学药学院,宁夏银川750004 [2]宁夏医科大学回医药现代化教育部重点实验室,宁夏银川750004

出　　处：《中国医药工业杂志》2023年第4期569-576,共8页Chinese Journal of Pharmaceuticals

基　　金：宁夏回族自治区重点研发计划项目(2021BEG02039)。

摘　　要：为改善美洛昔康(1)的水溶性,该研究采用超声辅助沉淀法制备其纳米混悬液,并采用单因素试验优化了处方和工艺参数。所得优化处方工艺为:以0.2%的泊洛沙姆188和0.2%的羟丙甲纤维素作为联合稳定剂,水、油两相体积比为30∶1,超声功率比为50%,超声35 min。制备的1纳米混悬液粒径为263.8 nm,多分散性指数(PDI)为0.189,ζ电位为–20.54 mV。将所得纳米混悬液冻干粉末复溶后,药物颗粒的粒径和PDI相比冻干前增大、ζ电位减小。透射电镜(TEM)、X射线衍射法(XRD)表征结果显示,纳米混悬液中1以原晶体的形式存在。分子动力学模拟结果显示,药物、泊洛沙姆188和羟丙甲纤维素之间形成了分子间氢键。体外溶出试验结果显示,1纳米混悬液在pH 6.0和pH 6.8的磷酸盐缓冲液中的溶出速度和程度明显高于原料药及其与联合稳定剂的物理混合物。To improve the water solubility of meloxicam(1),its nanosuspension was prepared by ultrasonicassisted precipitation method.The formulation and process parameters were optimized by single factor test.The optimal formulation process was as follows:0.2%of poloxamer 188 and 0.2%of hydroxypropyl methylcellulose(HPMC)were used as the combined stabilizers,the volume ratio of water to oil phase was 30∶1,the ultrasonic power ratio was 50%,and the ultrasonic time was 35 min.The particle size,polydispersity index(PDI)andζpotential of the optimal 1 nanosuspension were 263.8 nm,0.189 and–20.54 mV,respectively.After reconstruction of the freeze-dried powder of 1 nanosuspension,the particle size and PDI increased whileζpotential decreased compared with the 1 nanosuspension before lyophilization.The results of transmission electron microscopy(TEM)and X-ray diffraction(XRD)showed that 1 existed in the form of original crystal in the nanosuspension.The molecular dynamic simulation results showed that intermolecular hydrogen bonds were formed between the drug,poloxamer 188,and HPMC.The in vitro dissolution results showed that the dissolution rate and degree of 1 from the nanosuspension in pH 6.0 and pH 6.8 phosphate buffer solutions were significantly higher than those of the bulk drug and its physical mixture with the combined stabilizers.

关 键 词：美洛昔康 超声辅助沉淀法 纳米混悬液 分子动力学模拟 体外溶出 

分 类 号：R944.16[医药卫生—药剂学]