张英　张洪　彭锐

[摘要] 目的 研究索拉非尼纳米混悬剂的物理稳定性和化学稳定性。 方法 观察不同温度和时间下纳米混悬剂的粒径和多分散指数（PDI）的变化，并用HPLC对不同时间内索拉非尼纳米混悬剂的浓度进行测定并绘制其降解曲线。 结果 索拉非尼纳米混悬剂避光放于4℃下物理稳定性良好，粒径和PDI变化不大；索拉非尼纳米混悬剂与溶解状态的索拉非尼相比，化学稳定性显著改善，有效药物浓度的降解速度明显降低。 结论 将索拉非尼制成纳米混悬剂稳定性显著改善，可长期保存。

[关键词] 索拉非尼；纳米混悬剂；物理稳定性；化学稳定性

[中图分类号] R965 [文献标识码] A [文章编号] 1673-7210（2015）05（c）-0120-04

[Abstract] Objective To investigate the physical stability and chemical stability of Sorafenib Nanosuspension. Methods The change of size and PDI under different temperature and time were observed. The concentration of Sorafenib in different time was determined by using HPLC and its degradation curve was drawed. Results Sorafenib Nanosuspensions had little change in particle size and PDI， had a good physical stability in the dark at 4℃. The degradation rate of Sorafenib Nanosuspension highly decreased compared with the reference methanol solution of Sorafenib， which meant the good chemical stability of Sorafenib Nanosuspension. Conclusion The stability of Sorafenib can be improved significantly when it is prepared to nanosuspension. It can be long-term preserved.

[Key words] Sorafenib； Nanosuspension； Physical stability； Chemical stability

索拉非尼是一种新型二芳基脲类和口服多靶点分子靶向药物[1]，它的问世开创了进展期肝细胞癌系统治疗的里程碑[2-3]。它可以通过抑制血管内皮生长因子受体-2、FLT3、Ret、c-Kit受体酪氨酸激酶和血小板衍生生长因子受体而起作用，可阻断肿瘤细胞增殖和血管形成[4-6]。索拉非尼在临床上的应用主要为片剂，但是因其药物分子难溶于水，生物利用度低，副作用较严重，限制了其在临床上的应用。

纳米混悬剂是采用少量表面活性剂稳定药物粒子所形成的一种亚微米胶体分散体系，是一种分散度极好的固体药物粒子水分散体系[7]。常采用高分子聚合物作为载体来增加药物的溶解度和生物利用度[8-9]。目前已广泛应用于各种给药途径（口服、静注、肺部、经皮和眼部给药等）制剂的制备[10-12]。……