The continuing research and use of co-crystallisation for separation, purification and modification of pharmaceutical materials in multiple industrial sectors can be attributed to the potential for high control of product quality attributes. Nucleation is a key phenomenon in crystallisation that can control product purity, morphology and crystal size distribution. Despite the use of co-crystallisation in manner mentioned above, not a lot is known about nucleation kinetics in multicomponent systems. This thesis aims to identify gaps in knowledge and presents useful tools and methods pertinent to co-crystallisation in three themes. The first part deals with co-crystallisation within the scope of identifying factors that influence co-crystal solubility phase diagram (Chapter 3) in a workflow. Co-crystal screening methods is considered with the objective to compare and contrast approaches to increase chances of forming a co-crystal and extend an already established co-crystal screening workflow (Chapter 4). The third part addresses nucleation kinetics in multicomponent systems. Once the phase diagram is elucidated the effect of solution stoichiometry on nucleation kinetics in ternary systems is then investigated (Chapter 5). In a move to increase our knowledge of heterogeneous nucleation, a new approach to determine induction time through thermal changes when transmission of light is not reliable was developed and used to measure nucleation rates of small organic molecules (Chapter 6). Therefore, scaling previous experimental limitations and opening up new opportunities for co-crystal studies. The author is confident that the workflow developed for co-crystal phase diagram and heterogeneous nucleation method presented in this thesis would benefit future research in cocrystal nucleation from solution by informing experimental design and experimental configuration.
|Date of Award||2 Jun 2020|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council) & University of Strathclyde|
|Supervisor||Joop Ter Horst (Supervisor), Alastair Florence (Supervisor) & Jan Sefcik (Supervisor)|