CAJ | 학술논문

以黄芩素-烟酰胺共晶为模型药物，研究共晶形成的热力学。通过测定不同温度下黄芩素在不同浓度烟酰胺溶液中的溶解度，探讨黄芩素-烟酰胺共晶的络合形式，计算相关热力学参数，并绘制不同温度下的黄芩素-烟酰胺-乙酸乙酯三元相图。结果表明，黄芩素-烟酰胺共晶在乙酸乙酯中符合物质的量比1∶1溶液络合模型，共晶形成反应为热力学自发反应（ΔG°＜0），随着温度升高，Ksp逐渐增大，K11逐渐减小，反应自发程度减弱，三元相图中共晶区域减小，当温度达到T*＝315 K后，ΔG°＝0（ΔH°＝－6.314×10－2 kJ／mol，ΔS°＝－0.2005 J／mol· K），自发反应不再进行，证明低温有利于共晶的形成。根据三元相图的非对称特点，设计了3种不以物质的量比1∶1为出发点制备共晶的方法，DSC结果表明，3种方法制备得到的黄芩素-烟酰胺共晶均为熔点单一的纯共晶。
이황금소-연선알공정위모형약물，연구공정형성적열역학。통과측정불동온도하황금소재불동농도연선알용액중적용해도，탐토황금소-연선알공정적락합형식，계산상관열역학삼수，병회제불동온도하적황금소-연선알-을산을지삼원상도。결과표명，황금소-연선알공정재을산을지중부합물질적량비1∶1용액락합모형，공정형성반응위열역학자발반응（ΔG°＜0），수착온도승고，Ksp축점증대，K11축점감소，반응자발정도감약，삼원상도중공정구역감소，당온도체도T*＝315 K후，ΔG°＝0（ΔH°＝－6.314×10－2 kJ／mol，ΔS°＝－0.2005 J／mol· K），자발반응불재진행，증명저온유리우공정적형성。근거삼원상도적비대칭특점，설계료3충불이물질적량비1∶1위출발점제비공정적방법，DSC결과표명，3충방법제비득도적황금소-연선알공정균위용점단일적순공정。
Baicalein-nicotinamide(BE-NCT)co-crystal was chosen as model drug to investigate the thermody-namic characteristics.Solubilities of BE in NCT solutions in ethyl acetate at different temperatures were deter-mined in order to explain the complexation behavior of BE-NCT co-crystal.Thermodynamic parameters of co-crys-tal formation progress were calculated.Ternary phase diagrams (TPDs)of the BE-NCT-ethyl acetate systems at various temperatures were established.The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT co-crystal demonstrated a good correlation between calculated and experimental data (R2 >0.98). Co-crystal formation is a spontaneous process(ΔG°<0).Increase in temperature resulted in the increase of Ksp;decrease of K11 and a narrowed co-crystal zone.The degree of spontaneous reaction also decreased with increased temperature.The spontaneous reaction no longer carried out if the temperature reached T* =315 K sinceΔG°=0(ΔH°=-6.314 ×10 -2 kJ/mol;ΔS°=-0.200 5 J/mol.K).A drop in temperature favors the complexation between BE and NCT in ethyl acetate.Since NCT has higher solubility than BE in ethyl acetate;the TPDs of co-crystal was asymmetric.The DSC diagrams of products prepared via three presupposed methods confirmed that the BE-NCT co-crystal could be generated in solutions of nonstoichiometric compositions.