Modeling and Simulation Studies of a Novel Coupled Plug Flow Crystallizer for the Continuous Separation of Conglomerate-Forming Enantiomers

Abstract

Separation of enantiomers is a major concern in pharmaceutical industries due to the different therapeutic activities exhibited by the enantiomers. Preferential crystallization is an attractive means to separate the conglomerate-forming enantiomers. In this work, a simulation study is presented for a proposed novel preferential crystallization configuration that involves coupled plug flow crystallizers (PFCs). The PFCs are coupled through liquid phase exchange which helps the enrichment of the preferred enantiomer in the liquid phase. A set of coupled population balance equations (PBEs) are used to describe the evolution of the crystal size distribution (CSD) in the PFCs. The PBEs and the relevant mass balance equations are solved using the high-resolution finite-volume method. The simulation results predict that the proposed configuration has higher productivity compared to the currently used crystallization configurations while maintaining the same level of purity. Moreover, the effect of process variables, such as the extent of liquid phase change and the location of the PFC where liquid phase exchange occurs, are studied. The insights obtained from this simulation study will be useful in design, development, and optimization of such novel crystallization platforms.

Amplification of enantiomeric excess by dynamic inversion of enantiomers in deracemization of Au38 clusters

“…In addition, recently many emerging technologies have also been developed to achieve this goal. Crystallisation of a racemic mixture is an effective approach to enrich one enantiomer by the formation of conglomerate crystals 24 , 25 or through spontaneous deracemization during crystallisation 26 , 27 . Futhermore, coherent laser light 28 and highly enantioselective enzymes 29 have been used for efficient deracemization.…”

Complete chiral resolution in a continuous flow crystallizer with recycle stream

“…Several groups have studied the behaviour of the process of temperature-cycling-induced deracemization, either experimentally or computationally via the use of population balance equations. While earlier experimental studies relied on simple first-order kinetics expressions to describe the progress and the time-evolution of the enantiomeric excess [8], later more detailed models using population balance equations have been developed [10][11][12][13]. In the context of this work, we were looking for a simple way to quantify the efficiency of the deracemization process depending on the process settings of individual trials and relate it to the number of cycles performed.…”

Semi-continuous and continuous processes for enantiomeric separation

“…7). 91 Recently, Cameli et al 54 reported the continuous preferential crystallization of isoindoline-1-ones derivatives using a plug flow crystallizer immersed in two thermostatic baths set at different temperatures. This configuration allowed them to obtain productivities of 20 g L −1 h −1 due to the excellent heat transfer and low residence periods (Table 4 and Fig.…”