Model supported analysis and synthesis of a new process for continuous separation of enantiomers

对映不纯产品的提供对制药工业和生物技术提出了重大挑战。在适用于难对映体分离的技术中，选择性结晶技术尤其具有吸引力。到目前为止，主要采用的是间歇式工艺，很少有系统的方法来合理地开发连续对映选择性结晶工艺。本项目研究了一种使连续对映选择性结晶成为可能的工艺。优选地将每一种对映体结晶到两个锥形管状流化床结晶器之一中。为了最佳地利用驱动力，两个结晶器通过流体相耦合。第一次成功的实验证明了该工艺的可行性。为了对复杂的整体多步骤过程（混合、生长、成核、固液分离、粉碎）进行定量评价，建立了具有不同详细程度的数学模型，并进行了理论分析。采用cfd - dem模型，建立简化模型。对不同物质进行了理论过程分析。为了模拟整个过程，进行了CFD-DEM和简化模型的模拟。开发的详细和简化的模型将在本项目的第三阶段应用和评估，以确定依赖于物质的结晶器的最佳几何形状。经过验证的模型和获得的经验将与参与DFG优先计划的其他工作组分享。

The provision of enantiopure products poses a significant challenge for the pharmaceutical industry and biotechnology. Among the techniques applicable to difficult enantioseparations, selective crystallization techniques are particularly attractive. So far, primarily batch processes are used and there are few systematic approaches to the rational development of continuous enantioselective crystallization processes. With this project a process is studied, which enables continuous enantioselective crystallization. Each of the enantiomers is preferably crystallized into one of two conically shaped tubular fluidized bed crystallizers. For an optimal use of the driving force the two crystallizers are coupled via the fluid phase. First successful experiments carried out demonstrated the feasibility of the process. For the quantitative evaluation of the complex overall multi-step process (mixing, growth, nucleation, solid-liquid separation, comminution), mathematical models with different levels of detail have been developed and a theoretical analysis has been done. CFD-DEM-models were used and reduced models were developed. Theoretical process analysis has been performed for different substances. In order to simulate the whole process both CFD-DEM and reduced model simulations have been performed. The developed detailed and reduced models will be applied and evaluated in the third phase of this project in order to identify substance-dependent optimal geometries of the crystallizer. The validated models and the experiences acquired will be shared with other working groups participating in the DFG priority program.