论文部分内容阅读
目的采用反溶剂结合湿法研磨技术制备稳定的阿立哌唑混悬注射剂。方法将阿立哌唑原料药采用反溶剂法进行前处理后得到棒状的阿立哌唑晶体,将精制后的阿立哌唑进行湿法研磨,用激光粒度测定仪测定混悬液中颗粒大小随研磨时间的变化,筛选颗粒d50在1.9~2.2μm内需要的研磨时间;筛选不同的冻干保护剂,以冻干前后的粒径大小和分布为指标,得到最优的冻干保护剂。结果阿立哌唑混悬液在进行湿法研磨15 min后得到粒径d50为2.109μm,分布跨度为1.942的混悬液。甘露醇作为最优的冻干保护剂,冻干复溶后混悬液中颗粒大小和分布与冻干前基本一致。结论采用反溶剂结合湿法研磨制备阿立哌唑混悬注射剂,以甘露醇为冻干保护剂,可以得到复溶状态良好且稳定性高的阿立哌唑混悬液。
Objective To prepare a stable suspension of aripiprazole by anti-solvent combined with wet grinding technique. Methods The aripiprazole crystals were obtained by pretreatment with antisolvent method. The refined aripiprazole was wet-milled. The particle size of the suspension was determined by laser particle sizer With the change of milling time, the grinding time required for particle d50 in the range of 1.9 ~ 2.2μm was screened. Different lyoprotectants were screened, and the size and distribution of particle size before and after lyophilization were selected as indexes to obtain the optimal lyoprotectant. Results Aripiprazole suspension was wet-milled for 15 min to obtain a suspension with a particle size d50 of 2.109 μm and a distribution span of 1.942. Mannitol as the best lyoprotectant, the size and distribution of the particles in the freeze-dried reconstituted solution are basically the same as before freeze-dried. Conclusion Aripiprazole suspension injection was prepared by anti-solvent combined with wet-grinding method. Mannitol was used as lyoprotectant to obtain the aripiprazole suspension in good reconstituted state with high stability.