缬沙坦纳米混悬剂的制备及固化

Preparation and Solidification of Valsartan Nano-Suspensions

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 mg·mL-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 r·min-1,制得混悬液药物含量为3.3 g·L-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AEROSIL（R）200,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 m3·min-1,雾化压力170 kPa,进液速度4 mL·min-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。

OBJECTIVE To prepare valsartan nano-suspensions and solidify the suspensions. METHODS Valsartau nano-sus- pensions were prepared by anti-solvent precipitation and high pressure homogenization, and the suspensions were solidified by drying process. RESULTS Anti-solvent precipitation was chosen to prepared valsartan nano-suspensions. Based on the screening formula- tions and technological parameters, the optimal formulation and technological parameter were as following：stabilizer was F127 with the mass concentration of 2 mg · mL - 1, the mass ratio of valsartan to stabilizer was 5： 3, the temperature was 10 - 25 ℃ , the mixing speed was 300 -600 r · min -1 , to obtain 3.3 g · L-1 valsartan nano-suspensions. A spray drying process was selected to solidify the suspen- sions. The optimal mass ratio of AEROSIL （R） 200 to valsartan in the suspensions was 2： 1. After adding AEROSIL（R） 200 to the suspen- sions, the mixture was completely mixed for 30 min. The spray drying process parameters ：the inlet temperature was 110 ℃, the outlet tem- perature was 60 -65 ℃, the dry air flow rate was 0. 5 m3 · min -1, the spray pressure was 170 kPa, the feed liquor flow rate was 4 mL· min-1. CONCLUSION The mean diameter of the valsarlan 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.