尼群地平缓释微球的制备及其体内外相关性的研究

Preparation and correlation between in vitro release and in vivo absorption characteristics of sustained-release nitrendipine microspheres

目的制备具有固体分散体结构的尼群地平缓释微球 ,并筛选具有良好体内外相关性的释放介质。方法采用球晶造粒法制备尼群地平缓释微球 ,考察微球的粒径、载药量、包封率及释放行为 ,并根据 6只试验犬体内药物动力学试验结果 ,将不同时间的吸收分数与不同释放介质的相应时间点的体外累积释放百分数作线性回归 ,筛选具有良好体内外相关性的释放介质。结果制备的微球的粒径随搅拌速度的增加而减少 ,包封率均在 96 80 %以上 ,药物从微球中的释放速度随处方中固体分散体载体量的增加而增加 ,随阻滞剂量的增加而减小。以 1 7 4mmol L十二烷基硫酸钠为释放介质时 ,体外累积释放百分数与体内吸收分数相关系数较好 (r =0 985 1 ) ,方程为Fa =1 64 5 8ft-2 7 64 2。结论该方法较适用于难溶性药物制备缓释微球。以 1 7 4mmol

Objective To prepare the sustained-release nitrendipine microspheres having solid dispersion structures and to screen the dissolution medium with good in vitro and in vivo correlation for quality control.Methods The sustained-release nitrendipine microspheres were prepared by the spherical crystallization technique and the resultant microspheres were evaluated for the particle size,drug loading,incorporation efficiency and release rate.According to the results of pharmacokinetics in 6 dogs,the dissolution medium with good in vitro and in vivo correlation was screened by comparing the linear regressive equations between the absorption percentage in vivo and the accumulate dissolution percentage in vitro of nitrendipine in different dissolution mediums.Results The sizes of the resultant microspheres were decreased by increasing the agitation speed and the incorporation efficiency of nitrendipine was usually more than 96.8 %.The drug release rate from microspheres was increased by increasing the amount of solid dispersion carriers,and decreased by increasing the amount of retarding agents formulated.The good correlation coefficient ( r=0.985 1) can be obtained between the absorption percentage in vivo and accumulation dissolution percentage in vitro when the 17.4 mmol/L sodium dodecyl sulfate solution is employed as the dissolution medium.The equation is F a= 1.645 8f t-27.642.Conclusions The present method is useful for poorly soluble drug to prepare sustained-release microspheres and the 17.4 mmol/L sodium dodecyl sulfate solution,as a dissolution medium,can be employed to control the quality of sustained-release nitrendipine microspheres.