Chirally Discriminant Process Analytical Technologies

Abstract

Enantiomeric purity is of prime importance for several industries, specifically in the production of pharmaceuticals. It is crucial for enantiomers to be available in pure form because it can show different interactions with the living organism, one can be beneficial, while the other ineffective or even toxic to humans. Crystallization is one of the most effective chiral separation and purification process, however, some process variants inherently rely on kinetic entrainment (preferential crystallization) of the desired enantiomer or on complex interactions of several phenomena (e.g., attrition-enhanced deracemization, Viedma ripening). Thus, a process analytical technology PAT able to measure the enantiomeric composition of both the solid and liquid phase would be valuable to track and eventually control processes. This study presents a design and development of a novel automated analytical monitoring setup that achieves this purpose. The designed setup tracks the enantiomeric excess (ee) using a continuous closed-loop sampling system that is coupled to a polarimeter and an ATR-FTIR spectrometer. By heating the sampling loop and alternately sampling exclusively the liquid or the suspension, the combination of these measurements allows tracking the enantiomeric excess of both the liquid and the solid. This work demonstrates a proof of concept of both the experimental and theoretical aspects of the new system. The setup operates as a heated dissolution loop in a plug flow manner, thus, the separate analysis conducted with the coupled stirred vessels system aided in designing the deracemization process to be conducted in the continuous sampling setup. The developed experimental knowledge and process from the sampling setup can be combined and utilized later to optimize and control chiral resolution process through timely measurements of inprocess materials, and final products.

Date of Award	31 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Roger Davey (Supervisor) & Philip Martin (Supervisor)