泊那替尼纳米混悬剂的表面活性剂筛选及其稳定性考察

Surfactant screening and stability investigation of ponatinib nanosuspension

目的:对泊那替尼纳米混悬剂的表面活性剂的筛选及其稳定性研究。方法:采用聚乙烯吡咯烷酮(PVP K30)、泊洛沙姆P188、聚乙烯醇、磷脂和聚山梨酯-80为表面活性剂制备的泊那替尼纳米混悬剂;利用激光纳米粒度仪测定长期放置混悬剂中纳米粒子的平均粒径和多分散系数(PDI),Zeta电位分析仪测定其Zeta电位,高效液相色谱法(HPLC)对不同时间混悬剂中泊那替尼的浓度进行定量测定,绘出其降解曲线。结果:通过形态观察,以PVP K30为表面活性剂制备的混悬剂大小均匀、有乳光,且无针状结晶析出;与溶解状态下的泊那替尼相比,泊那替尼纳米混悬剂的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:采用PVP K30为表面活性剂制备的混悬剂稳定性较好,有望成为泊那替尼的新型纳米给药系统。

OBJECTIVE To prepare ponatinib nanosuspensions through different surfactants,screen optimal surfactant and investigate stability of ponatinib nanosuspensions. METHODS Ponatinib nanosuspensions were prepared with different surfactants,such as PVP K30,pluronic F-68,polyvinyl alcohol,phospholipid and tween 80. Mean size,polydipersity index and Zeta potential were determined using dynamic light scattering and zeta potential analyzer,respectively. Concentrations of ponatinib for different time points,and density was investigated by high performance liquid chromatography（ HPLC）. RESULTS Through morphology observation,only nanosuspensions prepared with PVP K30 presented size uniformity,opalescence,without needle crystal precipitation. Degradation rate was highly decreased for ponatinib nanosuspensions compared with reference methanol solution of ponatinib,suggesting good chemical stability of ponatinib nanosuspensions. CONCLUSION Stability of ponatinib nanosuspensions with PVP K30 surfactants and formulation may be a novel vehicle for injection of ponatinib.