| The objective of this dissertation is to develop mathematical methods to assist in the development of continuous processes for the manufacture of pharmaceutical drug products. Specifically, modeling, analysis and optimization techniques will be developed in order to apply concepts from the field of process systems engineering to pharmaceutical development. These concepts, including sensitivity analysis, feasibility and flexibility analysis and optimal design under uncertainty, can contribute to the development of robust and well-understood manufacturing processes. This is consistent with the aim Quality-by-Design in the pharmaceutical process development. Throughout this dissertation, case studies related to continuous solids-based manufacturing will be used to demonstrate the role that process systems engineering can play in process development. The mathematical methods introduced in this dissertation will emphasize the use of reduced-order and surrogate models to address the unique challenges associated with modeling, analysis and optimization of solids-based processes. |
