高载药量尼莫地平固体分散体的制备及其性能表征

Preparation and Characterization of Nimodipine Solid Dispersions with High Drug-loading

将尼莫地平与聚合物载体照质量比4∶1混合,采用热压挤出法制备了高载药量尼莫地平固体分散体。以制品在pH 1.0盐酸中的溶出行为为评价指标,优化了载体材料种类、挤出转速、挤出温度和制备方法。结果显示,在远低于尼莫地平熔点的80℃条件下,以30 r/min的转速通过热压挤出法制备的高载药量尼莫地平-Eudragit®EPO固体分散体,能显著提高尼莫地平的溶出度,15 min溶出率达80%以上。差示扫描量热、粉末X射线衍射、粒径测定和扫描电镜表征结果显示,固体分散体中药物以纳米晶形式存在。加速稳定性试验中,固体分散体中的尼莫地平由晶型Ⅰ转变为晶型Ⅱ,但体外溶出行为基本不变。

A high drug-loading solid dispersion of nimodipine was prepared via a hot-pressing extrusion method by mixing the bulk drug and a polymer carrier in a mass ratio of 4∶1.The process parameters,namely the carrier material type,rotational speed of the extrusion machine,extrusion temperature,and preparation method,were optimized with the dissolution behavior of the product in hydrochloric acid(pH 1.0)as the evaluation indicator.The results showed that the high drug-loading solid dispersions with Eudragit®EPO as the carrier prepared at 80℃which was far below the melting point of nimodipine and the rotational speed of 30 r/min by hot-pressing extrusion method could significantly improve the dissolution of nimodipine.The dissolution rate at 15 min was over 80%.The characteristic results of differential scanning calorimetry,powder X-ray diffraction,particle size determination and scanning electron microscopy showed that nimodipine was existed in the form of nanocrystals in the solid dispersion.In the accelerated test,nimodipine in the solid dispersion changed from crystal formⅠto crystal formⅡ,but the dissolution behavior in vitro remained basically unchanged.