伊曲康唑纳米晶体的制备与表征  

Preparation and characterisation of itraconazole nanocrystals

作　　者：戎欣玉[1,2] 宋红岩[1] 王慧春[1] 李志远[1] 赵涵[1] 高倩[1] 

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]河北省药物化工工程技术研究中心,河北石家庄050018

出　　处：《中国医院药学杂志》2017年第10期916-921,共6页Chinese Journal of Hospital Pharmacy

基　　金：河北省自然科学基金资助项目(编号:H2014208151);河北省高等学校科学技术研究项目(编号:ZD2014079)

摘　　要：目的:制备伊曲康唑纳米晶体并进行药剂学性质表征。方法:采用湿法介质研磨结合冷冻干燥工艺制备伊曲康唑纳米晶体;采用马尔文激光粒度测定仪测定伊曲康唑纳米晶体的粒径和多分散系数(PDI);采用扫描电镜观察伊曲康唑粒子的形态;采用差示扫描量热法、红外光谱法、X-射线粉末衍射法研究伊曲康唑纳米化前后晶型和化学结构变化情况;采用浆法比较伊曲康唑纳米化前后及市售胶囊在pH1.2、pH4.0、pH6.8的溶液以及水等4种溶出介质中的溶出行为。结果:制备的伊曲康唑纳米晶体平均粒径为317 nm,PDI值0.29;纳米化前后伊曲康唑晶型和化学结构没有发生明显改变;在pH1.2、pH4.0、pH6.8的溶液以及水等4种溶出介质中,药物溶出速率快慢顺序为伊曲康唑纳米晶体>市售伊曲康唑胶囊>物理混合物及伊曲康唑原料药。结论:采用湿法介质研磨结合冷冻干燥工艺,可以制备平均粒径小且较为均匀的伊曲康唑纳米晶体;纳米化后伊曲康唑仍为结晶态;制成纳米晶体可以明显改善伊曲康唑的溶出性能,利于改善药物的口服吸收。OBJECTIVE To prepare and investigate the pharmaceutical characteristics of itraconazole （ITZ） nanocrystals. METHODS ITZ nanocrystals were prepared by wet milling combined with freeze drying method. The size and polydispersity index （PDI） of ITZ nanocrystals were analyzed by melvin Zetasizer. The morphology of the nanocrystals was observed by scanning electron microscopy. The crystalline state and chemical structure of particles before and after nanonization were characterized by differential scanning calorimeter, infrared spectroscopy and X-ray powder diffraction. Dissolution behaviors of ITZ before and after nanonization and commercial ITZ capsules were studied using paddle method, and HCl aqueous solution （pH 1.2）, acetate buffer （pH 4. 0）, phosphatic buffer （pH 6. 8） and deionized water were used as the dissolution media. RESULTS The mean particle size and PDI of ITZ nanocrystals were 317 nm and 0. 29. Before and after nanonization, the crystalline state and chemical structure of ITZ were not obviously altered. In dissolution media mentioned above, the order of dissolution rate was ITZ nanocrystals 〉 commercial ITZ capsules 〉 physical mixture and bulk ITZ. CONCLUSION Wet milling combined with freeze drying process can produce ITZ nanocrystals with tiny and uniform particle size. After nanonization, ITZ is still crystal- line, and the dissolution is significantly increased, this is beneficial for improving the ITZ oral absorption.

关 键 词：伊曲康唑 纳米晶体 介质研磨 冷冻干燥 药剂学性质 

分 类 号：R943[医药卫生—药剂学]