热熔造粒法制备阿戈美拉汀多孔吸附物及其表征

Preparation and Characterization of Agomelatine Porous Adsorbents by Hot-melt Granulation

以阿戈美拉汀(1)为模型药物,交联聚维酮(PVPP)为载体,采用热熔造粒法制备1多孔吸附物(1-PA),并用粉末X射线衍射法(PXRD)和扫描电镜(SEM)进行表征。结果表明,药物主要以无定形态存在于多孔吸附物中。pH 2.0盐酸、pH 4.5乙酸盐缓冲液和pH 6.8磷酸盐缓冲液介质中,1原料药的溶解度分别为0.27、0.29和0.30 mg/ml,1-PA中1溶解度提升到0.40、0.41和0.40 mg/ml。在pH 2.0盐酸中初始30 min内,1-PA的溶出速度和程度明显高于物理混合物和原料药。并且,含量和有关物质测定结果表明,吸附物制备过程中,药物均被吸附,且有关物质没有显著上升(P>0.05)。另外,1-PA采用铝袋包装,在40℃、相对湿度75%下放置6个月后,溶解度、溶出度、含量和有关物质均无明显变化,提示制品具有良好的物理和化学稳定性。

The agomelatine （1） porous adsorbents with crospovidone （PVPP） as carriers, named as 1-PA, were prepared by hot-melt granulation and characterized by power X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The results showed that drug mainly existed in an amorphous form in porous adsorbents. The solubilities of the bulk drug in pH 2.0 hydrochloric acid solution, pH4.5 acetate buffer and pH6.8 phosphate buffer were 0.27, 0.29 and 0.30 mg/ml, while the solubilities of 1 in 1-PA increased to 0.40, 0.41 and 0.40 mg/ml, respectively. The dissolution rate and extent of 1 from 1-PA were significantly higher than those in physical mixture and bulk drug in pH 2.0 hydrochloric acid solution within initial 30 min. Moreover, the determination results of assay and related substances showed that almost all of the drug were adsorbed during the preparation process and its related substances were not significantly increased （P〉0.05）. In addition, the stability of the 1-PA packaged in aluminum bags and stored at 40 ℃ and relative humidity of 75% for 6 months was investigated. The results showed that the solubility, dissolution, determination results of assay and related substances had no significant changes, suggesting a good physical and chemical stability.