紫杉醇纳米晶混悬液的制备及表征

Preparation and Characterization of Paclitaxel Nanocrystalline Suspensions

目的对紫杉醇纳米晶混悬液的处方和制备工艺进行优化,对所优化的混悬液进行物理表征,并考察其体外释放特征。方法采用单因素试验法筛选高压均质机制备紫杉醇纳米晶混悬液的处方工艺;使用透射电镜等考察纳米晶外观形态、粒径分布;采用高效液相色谱法考察其平衡溶解度、体外释放特征。结果制备的纳米晶的平均粒径为(239.5±1.98)nm,PDI为0.111±0.011,Zeta电位为-(24.6±1.13)m V;电镜下紫杉醇纳米晶呈短棒状,均匀分布;纳米晶体在水和pH 7.4的PBS溶液中的平衡溶解度分别是原料药的1 800倍和250倍;在0.5%SDS-PBS(pH 7.4)溶液中紫杉醇纳米晶体5 min释放91.6%,物理混合物2 h释放67.7%。结论制备的紫杉醇纳米晶混悬液粒径分布均匀,处方简单,制备工艺简便可行,且显著提高了紫杉醇的溶解度和释放速率。

OBJECTIVE To optimize the formulation and preparation conditions of paclitaxel nanocrystalline suspensions, describe the physical characterization of paclitaxel nanocrystals, and inspect its in vitro release characteristics. METHODS Single factor experimental method was used to study the formulation composition and preparation procedure of paclitaxel nanocrystals to establish the preparation procedure of the method of high pressure homogenization. Nanocrystalline morphology, particle size distribution was physically characterized. An HPLC method was used to investigate the equilibrium solubility and in vitro release characteristics of paclitaxel nanocrystals. RESULTS The average particle diameter of nanocrystals was（239.5±1.98）nm, polydispersity was 0.111±0.011, Zeta electric potential was -（24.6±1.13）mV. TEM images showed that paclitaxel nanocrystals had a rod-like morphology with a uniform distribution. The equilibrium solubility of nanocrystals in PBS pH7.4 solution was 1 800 times as many as paclitaxel API and 250 times in water. In 0.5% SDS-PBS（pH 7.4） solution, the in vitro cumulative release of paclitaxel nanocrystals reached 91.6% in 5 min, while the cumulative release of physical mixture was 67.7% in 2 h. CONCLUSION The paclitaxel nanoparticles is distributed evenly, and the formulation and preparation method are simple and feasible. Nanocrystals significantly improve solubility and release rate of paclitaxel.