In pharmaceutical sector, compounds forming the drug and especially the active pharmaceutical ingredients (API's) are required to be pure, in accordance with the regulatory authorities' rules. The isolation stage is used to remove the impure liquid phase and to remove surface impurities from the crystalline product. Physico-chemical properties of crystals formed during the crystallization process and the solvents selected for the crystallization process influence the performance and the efficacy of isolation. Lots of effort was made in the last few decades to understand how to improve the crystallization stage. Relatively less effort has been made to understand the chemo-physical and process characteristics affecting the properties of the final isolated product.As consequence, the isolation stage can be responsible for extended API manufacturing time, the consumption of high quantities of materials and solvents and sometimes the requirement for isolated product post-processing to overcome variation of crystallized material properties caused by isolation.The aim of this thesis is to understand from a microscopic to a macroscopic point of view how the physic-chemical properties of the crystallized material and the washing solvents used in combination with the filtration, washing and drying approaches used can influence the final isolated product characteristics. To broaden the field, an alternative analytical technique for pharmaceutical field, TOF-SIMS, allows investigating the surface/subsurface of crystal to localize adsorption of related impurities to help to design isolation strategy and solvent selection.
|Date of Award||12 Dec 2018|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council)|
|Supervisor||Chris John Price (Supervisor) & Alison Nordon (Supervisor)|