The challenges of developing continuous crystallization processes of multicomponent crystals are addressed within this thesis. Multicomponent crystals such as co-crystals and solid solutions, can be used to modify physical properties of active pharmaceuticals, agrochemicals and other materials. These can result in enhanced product properties such as higher solubility, faster dissolution, better stability or improved manufacturability in downstream processing through desirable morphology and better powder flowability. Continuous manufacturing is routinely used in many industries but is a new trend in the manufacture of pharmaceuticals driven by the potential to reduce plant footprint and intermediate inventory, improve yields, reduce lead time, implement real time monitoring and automation and make processes safer.Compared to crystallization of single component crystals, additional component and solid phases introduce additional complexity in the phase diagram. Co-crystal phase diagram measurement in a series of solvents can be very time consuming compared to a solubility curve of a single component. A semi-empirical approach of modeling phase diagrams as well as new methods of measuring phase diagrams of multicomponent materials are presented to accelerate the time to obtain a phase diagram compared to traditional approaches. Transitions from small scale batch crystallization to continuous crystallization is also demonstrated here for co-crystals and solid solutions with high selectivity and reproducibility with respect to the solid phase produced.
|Date of Award||1 Oct 2018|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council)|
|Supervisor||Jan Sefcik (Supervisor) & Leo Lue (Supervisor)|