Combined cooling and antisolvent crystallization can improve the crystallization yield while reducing the consumption of antisolvent,which is an efficient coupled separation process.The interface of conventional mass transfer for antisolvent crystallization is often limited by the macroscopic mixing scale,and mass transfer regulation is usually sub-millimeter,which is prone to nucleation outbreaks,resulting in poor purity,small average size and wide crystal size distribution of crystalline products,thus requiring more precise regulation strategies.In this paper,a novel membrane-assisted combined cooling and antisolvent crystallization method was proposed and applied to the study of cefuroxime sodium crystallization process.Polytetrafluoroethylene(PTFE)hollow fiber membranes were used as an interface for precise addition of the antisolvent and efficient mixing to achieve a uniform distribution of supersaturation.To compare the regulation effects of membrane-assisted combined cooling and antisolvent crystallization with conventional crystallization method,the metastable zone width of the cefuroxime sodium-water-ethanol system with combined cooling and antisolvent crystallization under conventional and membrane-assisted conditions were measured and the nucleation kinetic parameters were calculated for precise regulation of the membrane assisted combined cooling and antisolvent crystallization process,respectively.The effects of cooling rate and antisolvent addition rate on the metastable zone width were analyzed using response surface methodology and theoretical models,and the metastable zone characteristics of conventional and membrane-assisted crystallization were compared.The results showed that the nucleation order and nucleation rate constant(n=2.07,kn=158.15)of membrane-assisted combined cooling and antisolvent crystallization were smaller than conventional crystallization(n=2.45,kn=493.22),and the nucleation process was gentler and more controllable.The research in this paper provides important basic theoretical data for further exploration of membrane-assisted combined cooling and antisolvent crystallization,and lays the foundation for crystallization process development and optimization.
关键词
膜辅助结晶/介稳区/溶析-冷却耦合结晶/过程强化/响应面方法
Key words
membrane-assisted crystallization/metastable zone/combined cooling and antisolvent crystallization/process intensification/response surface methodology
维普
万方数据