棕榈酸帕利哌酮单晶的制备及其结构表征  

Single crystal cultivate and crystal structure characterization of paliperidone palmitate

作　　者：周新波 刘继永[2] 俞卡茜[2] 胡秀荣 ZHOU Xin-bo;LIU Ji-yong;YU Ka-xi;HU Xiu-rong(Zhejiang Jingxin Pharmaceutical Co.,Ltd.,Shaoxing 312500,China;Department of Chemistry,Zhejiang University,Hangzhou 310028,China)

机构地区：[1]浙江京新药业股份有限公司,浙江绍兴312500 [2]浙江大学化学系,浙江杭州310028

出　　处：《现代药物与临床》2022年第7期1425-1431,共7页Drugs & Clinic

摘　　要：目的制备棕榈酸帕利哌酮单晶,进行结构表征。方法用溶液结晶法培养单晶,并用单晶X射线衍射仪检测分析;用多晶X射线衍射仪、差示扫描量热仪、热重分析仪和傅里叶变换红外光谱仪对晶体进行表征;用CrystalExplorer 17.5软件,以B3LYP/6-31G(d,p)波函数对棕榈酸帕利哌酮分子进行相互作用能的计算和分析。结果制备得到的棕榈酸帕利哌酮为无色条状晶体,该晶体属于单斜晶系,P21/c空间群,最小不对称单元中有1个棕榈酸帕利哌酮分子。TGA-DSC结果显示棕榈酸帕利哌酮晶体不含有溶剂/水分子,熔点峰顶值为117℃。相互作用能分析显示棕榈酸帕利哌酮分子间存在7种数值不同的相互作用能,总相互作用能之和为−574 kJ/mol。结论确证了棕榈酸帕利哌酮的晶体结构,为棕榈酸帕利哌酮的进一步开发提供了研究基础。Objective To cultivate single crystal of paliperidone palmitate,and to characterize the structure of paliperidone palmitate.Methods Solution crystallization method was applied to grow single crystal of paliperidone palmitate.The crystal structure of paliperidone palmitate was studied by single crystal X-ray diffraction(SXRD),powder X-ray diffraction(PXRD),thermogravimetric analysis(TGA),differential scanning calorimetry(DSC),and Fourier transform infrared spectrometer(IR).The interaction energy of paliperidone palmitate molecule calculated by B3LYP/6-31G(d,p)wave function with the aid of CrystalExplorer 17.5 software.Results Single colorless needle crystal of paliperidone palmitate could be obtained through solution crystallization method.SXRD results show that the crystal of paliperidone palmitate crystallized in the monoclinic space group P21/c,with one paliperidone palmitate molecule in the asymmetric unit.TGA-DSC results show that the crystal of paliperidone palmitate was un-solvated,and the melting point is 117°C.The result of interaction energy analysis is that 7 kinds of intermolecular interaction energies exist in paliperidone palmitate.The total interaction energy is-574 kJ/mol.Conclusion Crystal structure of paliperidone palmitate is characterized,which provides a basis for the further development of paliperidone palmitate.

关 键 词：棕榈酸帕利哌酮 晶体结构 X射线单晶衍射 能量框架 结构表征 

分 类 号：R914.2[医药卫生—药物化学]