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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。
A porous adsorbent (1-PA) was prepared by hot melt granulation using agomelatine (1) as a model drug and PVPP as a carrier. The results of powder X-ray diffraction (PXRD) And scanning electron microscopy (SEM). The results show that the drug exists mainly in amorphous state in the porous adsorbent. The solubility of 1 API in pH 2.0 HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer medium were 0.27, 0.29 and 0.30 mg / ml, respectively, and the solubility in 1-PA was increased to 0.40, 0.41 and 0.40 mg / ml. The dissolution rate and extent of 1-PA in the initial 30 min of pH 2.0 hydrochloric acid was significantly higher than that of the physical mixture and API. In addition, the determination of content and related substances showed that during the preparation of adsorbates, the drugs were all adsorbed and the related substances did not increase significantly (P> 0.05). In addition, 1-PA was packed in aluminum bags and its solubility, dissolution, content and related substances had no significant change after 6 months at 40 ℃ and relative humidity of 75%, suggesting that the product had good physical and chemical stability.