摘要：本研究针对Mei025的多晶型问题，采用不同的结晶条件和实验手段，系统地筛选了化合物Mei025可能的晶型。通过近300次的结晶实验和粉末X射线衍射、红外、热分析、动态蒸汽吸附表征发现，Mei025两种的晶体形式存在，为晶型A (原料)和无定型粉末。晶型A，是一种无水晶型，且非常稳定。以甲醇，乙醇，异丙醇、异戊醇、甲基叔丁基醚、甲苯、正己烷、正庚烷、乙醚、水为溶剂，进行混悬；25 °C单一溶剂和混合溶剂缓慢挥发挥发及50 °C单一溶剂和混合溶剂缓慢挥发；反溶剂和冷却结晶；将原料研磨成无定形后，再进行25 °C和50 °C混悬，这些实验条件下重析出晶型都为晶型A，表征试验阐明温度、湿度、溶剂对Mei025晶型影响不大。另一种是用二氯甲烷悬蒸研磨后获得的无定形的固体状态，室温空气放置2天以上部分转晶为晶型A。根据实验数据，晶型A具备许多优秀性质，包括结晶度、低吸湿性和稳定性等，所以推荐其为Mei025的优选药用晶型。77504
毕业论文关键词：多晶型；X射线粉末衍射（XPRD）；动态蒸汽吸附法（DVS）；差示扫描量热仪（DSC）；热重分析（TG）；结晶
The study of Mei025 polymorphs
Abstract: In this paper, the polycrystalline conditions of Mei025 were studied with different crystallization conditions and experimental methods。 We systematically select the possible crystalline form of the compound, Mei025。 By nearly 300 times of experiments and powder X-ray diffraction (XRD), infrared, thermal analysis, dynamic vapor adsorption characterization’s help, we found that Mei025 has two crystal forms, one is form A (raw material) and the other is amorphous powder。
The form A is a anhydrous crystal form and it is very stable。 When we use methanol, ethanol, isopropanol, isoamyl alcohol, methyl tert-butyl ether, toluene, n-hexane, n-heptane, diethyl ether, water as solvent, use method: 1。 Suspend Mei025 raw material into solutions above。 2。 slowly volatile solvent volatilization with 25 ° single solvents and mixed solvent and 50 ° C single and mixed solvent condition。 3。 Antisolvent crystallization。 4。cooling crystallization。 5。 After raw material grinding into amorphous, then use the product for 25 ° C and 50 ° C suspension。 Under all these five method, recrystallization experiment give form A(XPRD just like raw material) 。 Characterization experiment shows that temperature, humidity, solvent has little influence to Mei205。
We obtained amorphous powder by rotary evaporation with dichloromethane and grinding。 When the product placed at room temperature for more than two days, crystal phenomenon occur, it transfer to be form A 。
According to the experimental data, form A has good crystallinity, low moisture absorption and stability, so we recommended that it is a good choice for Mei025。
Key words: Polymorph；X-ray powder diffraction (XPRD); dynamic vapor adsorption (DVS); differential scanning calorimetry (DSC); thermogravimetric analysis (TG); crystallization
目录
1绪论1
1。1 研究目的1
1。2 结晶原理2
1。3 研究内容2
1。4 原料药质量要求3
2 正文·4
2。1 原料药的批次及物化参数4
2。2 实验仪器型号及在晶型方面的研究意义4
2。3 试剂名称纯度及生产公司5
2。4 实验方法· 5
2。4。1 混悬结晶6
2。4。2 挥发结晶7
2。4。3 缓慢降温结晶9
2。4。4 反溶剂结晶9
2。4。5 在加热和冷却时的相转变9
2。4。6 水吸附与解吸附实验· 9
2。4。7 研磨制备无定型后混悬实验9 Mei025的多晶型研究:http://www.youerw.com/huaxue/lunwen_89072.html