Systematic Investigations on Continuous Fluidized Bed Crystallization for Chiral Separation

Abstract

A recently developed continuous enantioseparation process utilizing two coupled fluidized bed crystallizers is systematically investigated to identify essential correlations between different operation parameters and the corresponding process performance on the example of asparagine monohydrate. Based on liquid phase composition and product crystal size distribution data, it is proven that steady state operation is achieved reproducibly in a relatively short time. The process outputs at steady state are compared for different feed flow rates, supersaturations, and crystallization temperatures. It is shown that purities >97% are achieved with productivities up to 40 g/L/h. The size distribution, which depends almost exclusively on the liquid flow rate, can be easily adjusted between 260 and 330 µm (mean size) with an almost constant standard deviation of ±55 µm.

Linear Analysis of a Continuous Crystallization Process for Enantiomer Separation

“…The other consequence is that the validity of the linear model is limited to shorter operation times. In experiments, a slow contamination of the product has not been found [8]. The purity of the product remained high for operation times of up to 10 h. The experimental purity is slightly lower than the simulated values, which may be explained by the uncertainties in the simulated nucleation rates, or by uncertainties in the measurements.…”

“…The feasibility of the process has been proven in experiments [5,7,8]. It was found that the operation window for successful separation is quite small.…”

“…The main focus used to be on productivity and the size distribution of the product crystals. The purity of the product has so far been less considered, one reason being that it is quite hard to obtain reliable kinetic expressions for nucleation, because the nucleation mechanisms in the process are not fully understood [8]. The objective of this work is to derive criteria for product purity that are easier to evaluate.…”

“…However, in reality, B varies due to the spatially varying supersaturation of the liquid phase. Further, experimental results in [8] indicate that the nucleation mainly takes place at the crystallizer walls and, therefore, may be different at different points in the crystallizer and may also change over time, when crystals adhere to the walls. A time and space dependent nucleation rate B(x, t) would hardly have an effect on the proposed solution approach for the linear model.…”

“…Figure 10. Comparison of the crystal phase purity in the linear model with the product purity in the detailed model from [7] and with the experimental product purity from [8]. The inset figure gives a close-up view of the experimental data.…”