热力学和动力学在三相伴随结晶中的相互作用  

Interaction between thermodynamics and kinetics in trimorphic concomitant crystallization

作　　者：兰金琦 朱振兴 谢闯[1] LAN Jinqi;ZHU Zhenxing;XIE Chuang(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;State Key Laboratory of Catalytic Materials and Reaction Engineering,RIPP,SINOPEC,Beijing 102200,China)

机构地区：[1]天津大学化工学院,天津300072 [2]石油化工催化材料与反应工程国家重点实验室,北京102200

出　　处：《化学工业与工程》2024年第6期149-157,共9页Chemical Industry and Engineering

基　　金：中国石油化工股份有限公司石油化工科学研究院开放基金课题(ZC0609-0005)

摘　　要：伴随多晶型是多种晶型同时析出的特殊现象,在制药过程中需尽力避免。针对磺胺噻唑在水中的三相伴随结晶行为,讨论了热力学和动力学相互作用对其影响。采用动态法测定了磺胺噻唑Form II/Ⅲ/Ⅳ在水中不同温度下的溶解度,表明在15~60℃内FormⅢ是热力学稳定晶型,FormⅡ和Ⅳ具有相似溶解度。测定了不同过饱和度下的成核诱导期和对应多晶型,发现在低过饱和度下(1.15≤S≤1.40),只析出FormⅢ,高过饱和度下(1.90≤S≤9.00)出现三相伴随结晶。动力学测定表明FormⅣ是动力学最优晶型,但Form II具有最小的临界晶核和成核能垒。动力学和热力学相互作用和竞争解释了上述伴随多晶型的过饱和度依赖关系。引入Ostwald比值预测了磺胺噻唑在水中伴随结晶的三元相图,量化了过饱和度对3种晶型比例的影响。Concomitant polymorphism is a special phenomenon of simultaneous crystallization of multiple polymorphs,which should be avoided in pharmaceutical process.The effects of thermodynamics-kinetics interaction on the trimorphic concomitant crystallization of sulfathiazole in water were discussed.The solubility of sulfathiazole Form II/III/IV in water at different temperatures was determined using dynamic method,indicating that Form III is a thermodynamically stable polymorph within 15—60℃,and Form II&IV have similar solubility.The nucleation induction period and corresponding polymorphs under different supersaturation were determined.It was found that pure Form III can be obtained at low supersaturation(1.15≤S≤1.40),while at high supersaturation(1.90≤S≤9.00)trimorphic concomitant crystallization occurs.Kinetics study shows that Form IV is the kinetically optimal polymorph,but Form II has the smallest critical radius and nucleation energy barriers.The interactions and competition of kinetic and thermodynamics can explain the above-mentioned supersaturation dependence of concomitant polymorphism.The Ostwald ratio was introduced to predict the ternary phase diagram of the concomitant crystallization of sulfathiazole in water,quantifying the effect of supersaturation on the ratio of the three concomitant polymorphs.

关 键 词：伴随多晶型 过饱和度 结晶热力学 成核 结晶动力学 

分 类 号：TQ028.5[化学工程]