Effect of Initial Conditions on Solid-State Deracemization via Temperature Cycles: A Model-Based Study

Solid-state deracemization via temperature cycles is a technique to obtain a pure powder of the desired enantiomer of a conglomerate forming compound from an initial mixture of both solid enantiomers, through a combination of dissolution and growth due to size-dependent solubility, in the presence of racemization in solution. The complexity of the process requires a mathematical model to understand the effect of initial conditions and operating parameters on the process outcome and performance. To this aim, we use our recently developed population balance based model of deracemization through temperature cycles to explain the large variations in deracemization time and in process outcome that are observed in experiments. We show how the direction of the evolution toward one or the other pure enantiomer is influenced by the initial asymmetries between the crystal populations of the two enantiomers. We observe how the process response varies to changes in the initial conditions and compare performance based on productivity. As for the operating conditions, we have performed simulations in the presence of attrition to investigate the effect of process conditions and system properties.