目的 制备并固化缬沙坦纳米混悬液。方法 采用反溶剂沉淀法和高压匀质法制备缬沙坦纳米混悬液,采用干燥法实现纳米混悬液固化。结果 在处方和工艺筛选基础上,确定反溶剂沉淀法为制备缬沙坦纳米混悬液的最终方法。工艺和处方为:稳定剂为F127,浓度为2 mgmL-1,药物与稳定剂比为5∶3(W/W),制备温度为10~25 ℃,搅拌速度为300~600 rmin-1,制得混悬液药物含量为3.3 gL-1。确定喷雾干燥法为缬沙坦纳米混悬液的干燥固化方法,其工艺为向缬沙坦纳米混悬液中加入缬沙坦2倍量的AEROSIL200,搅拌30 min,充分分散。喷雾干燥参数如下:进口温度110 ℃,出口温度60~65 ℃,干燥空气流速0.5 m3min-1,雾化压力170 kPa,进液速度4 mLmin-1。结论 缬沙坦纳米混悬液粒子平均粒径为30 nm,粒度分布均一;纳米混悬液经过喷雾干燥固体化后得到粉末细腻、疏松、流动性好、溶出度和稳定性良好,适合进一步制备固体制剂。
Abstract
OBJECTIVE To prepare valsartan nano-suspensions and solidify the suspensions. METHODS Valsartan nano-suspensions were prepared by anti-solvent precipitation and high pressure homogenization, and the suspensions were solidified by drying process. RESUTLS Anti-solvent precipitation was chosen to prepared valsartan nano-suspensions. Based on the screening formulations and technological parameters, the optimal formulation and technological parameter were as following:stabilizer was F127 with the mass concentration of 2 mgmL-1, the mass ratio of valsartan to stabilizer was 5∶3, the temperature was 10-25 ℃, the mixing speed was 300-600 rmin-1, to obtain 3.3 gL-1 valsartan nano-suspensions. A spray drying process was selected to solidify the suspensions. The optimal mass ratio of AEROSIL200 to valsartan in the suspensions was 2∶1. After adding AEROSIL200 to the suspensions, the mixture was completely mixed for 30 min. The spray drying process parameters:the inlet temperature was 110 ℃, the outlet temperature was 60-65 ℃, the dry air flow rate was 0.5 m3min-1, the spray pressure was 170 kPa, the feed liquor flow rate was 4 mLmin-1.CONCLUSION The mean diameter of the valsartan nano-suspensions was 30 nm and the diameter distribution was uniform.The dry valsartan nano-suspensions were fine and puff with good fluidity,dissolution and stability, suit to further preparation.
关键词
难溶药物 /
缬沙坦 /
纳米粒 /
纳米混悬剂
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Key words
poorly soluble drug /
valsartan /
nano-particle /
nano-suspension
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中图分类号：
R944
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参考文献
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脚注
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基金
国家973计划(2009CB930300);辽宁省教育厅重点实验室项目(LS2010161)
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