本文選題：熱熔造粒技術(shù) + 恩格列凈�。� 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：本課題采用熱熔造粒技術(shù)制備了恩格列凈-微晶纖維素組合物以及阿戈美拉汀-交聯(lián)聚維酮吸附物,分別對(duì)該技術(shù)提高藥物溶出速度和制備一種無(wú)定形藥物方面進(jìn)行了研究。在制備恩格列凈-微晶纖維素組合物,提高藥物溶出速度研究方面,選用微晶纖維素(MCC)為輔料,熱熔造粒法制備恩格列凈與微晶纖維素的組合物。組合物1、2、3中恩格列凈與微晶纖維素的質(zhì)量比分別為1：2、1：3和1：4。采用顯微鏡觀察組合物外觀,采用差示掃描量熱法(DSC)和粉末X射線衍射法(PXRD)對(duì)所得組合物進(jìn)行檢測(cè),并對(duì)比組合物和不同粒徑藥物的體外溶出速度。結(jié)果表明,DSC及PXRD圖譜確定了組合物中恩格列凈的存在形式是晶體與無(wú)定形的混合狀態(tài),體外溶出度實(shí)驗(yàn)表明其溶出速度能得到提升,組合物2和3的溶出速度與微粉化的原料藥溶出速度類似。說(shuō)明,采用熱熔造粒技術(shù)能有效提高藥物的溶出速度。在制備阿戈美拉汀-交聯(lián)聚維酮吸附物以獲得一種穩(wěn)定的無(wú)定形態(tài)藥物技術(shù)方面,以阿戈美拉汀為模型藥物,交聯(lián)聚維酮(PVPP)為載體,采用熱熔造粒法制備阿戈美拉汀多孔吸附物。采用PXRD對(duì)多孔吸附物進(jìn)行結(jié)構(gòu)表征,并采用掃描電鏡(SEM)觀察多孔吸附物外觀。結(jié)果表明,藥物主要以無(wú)定形態(tài)存在于多孔吸附物中。溶解度試驗(yàn)表明,pH2.0鹽酸溶液、pH4.5乙酸鹽緩沖液和pH6.8磷酸鹽緩沖液介質(zhì)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分別提升到0.40±0.01、0.41±0.02和0.40±0.02mg/m L,溶出曲線試驗(yàn)表明,30 min前吸附物溶出速度快于阿戈美拉汀原料藥,30 min后兩者接近。含量和有關(guān)物質(zhì)測(cè)定結(jié)果表明,吸附物制備過(guò)程中,藥物均被吸附,且有關(guān)物質(zhì)沒(méi)有顯著上升(P0.05)。另外,多孔吸附物在40℃/相對(duì)濕度75%下放置6個(gè)月后具有良好的物理和化學(xué)穩(wěn)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 鹵0.01g 0.29 鹵0.00 and 0.30 鹵0.01 mg/mL to 0.40 鹵0.01g 0.41 鹵0.02 and 0.40 鹵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，

本文編號(hào)：1735029