【摘要】 采用反溶剂沉淀法联合高压均质法技术制备塞来昔布的纳米晶体,提高其溶出度。以塞来昔布初混悬液形貌、纳米晶体混悬液粒子粒径和多分散系数(PDI)为指标,考察稳晶剂种类和比例、高压均质参数、固化方式等的影响。结果表明,将聚维酮K30 25 mg与十二烷基硫酸钠2.5 mg联用作稳晶剂,500 bar下循环10次,得到的纳米晶体粒径为(283.67±20.84)nm,PDI为0.16±0.01(n=3)。喷雾干燥得到的产品复溶后能分散成均一混悬液,粒径为(623.33±28.71)nm。采用X射线衍射、差示扫描量热法、扫描电镜、透射电镜、饱和溶解度对原药及纳米晶体性质进行表征分析,结果表明纳米晶体结构和晶型保持不变。所得纳米晶体的溶出率明显高于原药和物理混合物,且在高温高湿条件下放置10 d仍较稳定。更多还原

【Abstract】 Celecoxib nanocrystals were prepared by a combined method of antisolvent precipitation and high pressure homogenization to increase the dissolution of celecoxib. The effects of types and ratios of stabilizers, pressure and circle numbers of high pressure homogenization were investigated with appearance of initial suspension, particle size and polydisperse index(PDI) of nanocrystal suspension as indexes. The optimal nanosuspension was prepared with the combined stabilizers of 25 mg of Polyvidone K30 and 2.5 mg of sodium dodecyl sulfate, at the pressure of 500 bar for 10 circles. The particle size and PDI of the nanosuspension were(283.67±20.84) nm and 0.16±0.01(n=3). Then the nanosuspension was spray-dried to obtain the nanocrystals of celecoxib. The spray-dried product could redisperse rapidly to form uniform suspension with the particle size of(623.33±28.71)nm. The product was also characterized by X-ray diffraction, differential scanning calorimeter, scanning electron microscope, transmission electron microscope and saturated solubility. The results showed that the nanocrystals had the same chemical structure and crystalline form with celecoxib. The dissolution of the nanocrystals was signifi cantly higher than that of bulk drug and physical mixture. The product stored at high temperature and high moisture condition for 10 d was still rather stable.更多还原