热熔造粒技术在制剂中的应用和评价

发布时间：2018-04-11 07:35

  本文选题：热熔造粒技术 + 恩格列净　； 参考：《浙江大学》2017年硕士论文

【摘要】：本课题采用热熔造粒技术制备了恩格列净-微晶纤维素组合物以及阿戈美拉汀-交联聚维酮吸附物,分别对该技术提高药物溶出速度和制备一种无定形药物方面进行了研究。在制备恩格列净-微晶纤维素组合物,提高药物溶出速度研究方面,选用微晶纤维素(MCC)为辅料,热熔造粒法制备恩格列净与微晶纤维素的组合物。组合物1、2、3中恩格列净与微晶纤维素的质量比分别为1：2、1：3和1：4。采用显微镜观察组合物外观,采用差示扫描量热法(DSC)和粉末X射线衍射法(PXRD)对所得组合物进行检测,并对比组合物和不同粒径药物的体外溶出速度。结果表明,DSC及PXRD图谱确定了组合物中恩格列净的存在形式是晶体与无定形的混合状态,体外溶出度实验表明其溶出速度能得到提升,组合物2和3的溶出速度与微粉化的原料药溶出速度类似。说明,采用热熔造粒技术能有效提高药物的溶出速度。在制备阿戈美拉汀-交联聚维酮吸附物以获得一种稳定的无定形态药物技术方面,以阿戈美拉汀为模型药物,交联聚维酮(PVPP)为载体,采用热熔造粒法制备阿戈美拉汀多孔吸附物。采用PXRD对多孔吸附物进行结构表征,并采用扫描电镜(SEM)观察多孔吸附物外观。结果表明,药物主要以无定形态存在于多孔吸附物中。溶解度试验表明,pH2.0盐酸溶液、pH4.5乙酸盐缓冲液和pH6.8磷酸盐缓冲液介质中,吸附物中阿戈美拉汀溶解度由0.27±0.01、0.29±0.00和0.30±0.01 mg/mL分别提升到0.40±0.01、0.41±0.02和0.40±0.02mg/m L,溶出曲线试验表明,30 min前吸附物溶出速度快于阿戈美拉汀原料药,30 min后两者接近。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(P0.05)。另外,多孔吸附物在40℃/相对湿度75%下放置6个月后具有良好的物理和化学稳定性。
[Abstract]:In this paper, neglitazine-microcrystalline cellulose compositions and ameralatin-crosslinked polyvidone adsorbents were prepared by hot melt granulation technology. The study was carried out to improve the dissolution rate of the drug and to prepare an amorphous drug.In the aspect of preparing Englicnet-microcrystalline cellulose composition and improving drug dissolution rate, the composition of Englicnet and microcrystalline cellulose was prepared by hot melt granulation with microcrystalline cellulose (MCCs) as auxiliary material.The mass ratios of Engli net to microcrystalline cellulose in composition 1: 2 are 1: 2, 1: 3 and 1: 4, respectively.The appearance of the composition was observed by microscope. The composition was detected by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The dissolution rate of the composition was compared with that of drugs with different particle sizes in vitro.The results showed that the exiting form of Englicnet in the composition was a mixture of crystal and amorphous, and the dissolution rate of the compound was improved by dissolution experiments in vitro.The dissolution rate of compositions 2 and 3 is similar to that of micropowdered API.It shows that hot melt granulation technology can effectively improve the dissolution rate of drugs.In order to obtain a stable amorphous drug by preparing the adsorbents of agomelatin and crosslinked poly (viridol), the model drug was used as model drug, and the cross-linked polyvinylidene vinylidene (PVPP) was used as the carrier.The porous adsorbents of agomelatin were prepared by hot melt granulation.The structure of porous adsorbents was characterized by PXRD and the appearance of porous adsorbents was observed by scanning electron microscope (SEM).The results showed that the drug mainly existed in porous adsorbents in amorphous form.Solubility test showed that pH 2.0 hydrochloric acid solution, pH 4.5 acetate buffer and pH6.8 phosphate buffer medium,The solubility of amelatin increased from 0.27 卤0.01g 0.29 卤0.00 and 0.30 卤0.01 mg/mL to 0.40 卤0.01g 0.41 卤0.02 and 0.40 卤0.02mg/m L, respectively. The dissolution curve showed that the dissolution rate of the adsorbents before 30 min was faster than that after 30 min.The results of the determination of the contents and related substances showed that all the drugs were adsorbed during the preparation of the adsorbents, and the related substances did not increase significantly (P0.05).In addition, the porous adsorbents have good physical and chemical stability after being stored at 40 鈩，

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