雾化吸入用布地奈德纳米混悬液的制备及体外评价

Preparation and in vitro Evaluation of Budesonide Inhalation Nanosuspension

采用沉淀法制备布地奈德纳米晶体,以药物晶体平均粒径为指标,进行了工艺参数研究,以粒径<1μm的药物晶体累积百分数、稳定性和雾化性能为指标进行了雾化吸入用布地奈德纳米混悬液的处方筛选,最终制得平均粒径500~600 nm,粒径<1μm的药物粒子质量累积百分数为95%~100%的布地奈德纳米混悬液,40℃条件下的稳定性良好。采用新一代撞击器(NGI),考察了布地奈德纳米混悬液经Pari雾化器(喷射式雾化器)和自制振动网式雾化器雾化的雾化性能。结果显示Pari雾化器的药物递送剂量百分数为(39.50±4.27)%,空气动力学粒径小于5μm的粒子中累积药量占输出药量的百分比(FPF_(<5 μm))为(68.25±0.26)%;自制振动网式雾化器药物递送剂量百分数为(90.67±2.94)%,FPF_(<5μm)为(85.94±0.32)%。表明自制振动网式雾化器可显著提高药物的递送剂量,且微细粒子分数更高,提示布地奈德纳米混悬液经振动网式雾化器给药具有较好的开发前景。

Budesonide nanocrystals were prepared by precipitation method. The influences of various processing parameters such as crystallization temperature, stirring speed, addition speed of drug solution, budesonide concentration in ethanol and solvent to anti-solvent ratio, on the average particle size ofbudesonide nanocrystals were investigated. Then the formulation was optimized with the accumulated percentage of the particles less than 1 ktm, the stability and atomization performance of the nanosuspensions as indexes. The resulting budesonide inhalation nanosuspension had an average size of 500-600 nm and 95%-100% of the accumulated particles less than 1 ktm, which was stable for one month at 40 ~C. The atomization performance of the inhalation nanosuspension was evaluated using next generation impactor （NGI） atomized with Pari nebulizer and self-made vibrating-mesh nebulizer, respectively. The main evaluation parameters were delivered dose percentage, the drug amount in particles with the aerodynamic particle size smaller then 5.0 μm （FPF〈5μm）, and mass median aerodynamic diameter （MMAD）. The results showed that the recoveries of drugs for the Pari and self-made vibrating-mesh nebulizers were （96.53±4.24） % and （95.02±8.62） % respectively, and the percentage of delivered dose and FPF〈5 μm were （39.50±4.27） % and （68.25±0.26） % for Pari nebulizer, （90.67±2.94） % and （85.94±0.32） % for self-made vibrating-mesh nebulizer, respectively. It showed that the vibrating-mesh nebulizer could significantly improve the delivered dose and fine particle fraction, which was expected to reduce dosing volume, shorten treatment time and improve patient＇s compliance, indicating a good prospect for pulmonary drug delivery.