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

对映体产品的提供给制药业和生物技术带来了重大挑战。在适用于困难的对映体分离的技术中，选择性结晶技术尤其吸引人。到目前为止，主要使用间歇结晶过程，很少有系统的方法来合理开发连续的对映选择性结晶过程。利用该项目研究了一种能够实现连续对映体选择结晶的工艺。每个对映体优选地结晶成两个圆锥形管状流态化结晶器之一。为了最大限度地利用驱动力，两个结晶器通过流体相耦合。首先进行了成功的实验，证明了该工艺的可行性。为了定量评价复杂的整体多步骤过程(混合、生长、成核、固液分离、粉碎)，建立了不同细节层次的数学模型，并进行了理论分析。采用CFD-DEM模型，建立了简化模型。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模拟和简化模型模拟。开发的详细和简化的模型将在该项目的第三阶段中应用和评估，以确定结晶器的与物质相关的最佳几何形状。经验证的模型和获得的经验将与参与DFG优先方案的其他工作组分享。

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.