Date of Award
Fall 2014
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Aeronautics and Astronautics
First Advisor
Alina Alexeenko
Committee Chair
Alina Alexeenko
Committee Member 1
Elizabeth M. Topp
Committee Member 2
John P. Sullivan
Committee Member 3
Steven L. Nail
Abstract
Freeze-drying is a low-pressure, low-temperature condensation pumping process widely used in the manufacture of bio-pharmaceuticals for removal of solvents by sublimation. The goal of the process is to provide a stable dosage form by removing the solvent in such a way that the sensitive molecular structure of the active substance is least disturbed. The vacuum environment presents unique challenges for understanding and controlling heat and mass transfer in the process. As a result, the design of equipment and associated processes has been largely empirical, slow and inefficient.^ A comprehensive simulation framework to predict both, process and equipment performance is critical to improve current practice. A part of the dissertation is aimed at performing coupled fluid-thermal analysis of low-pressure sublimation-condensation processes typical of freeze-drying technologies. Both, experimental and computational models are used to first understand the key heat transfer modes during the process. A modeling and computational framework, validated with experiments for analysis of sublimation, water-vapor flow and condensation in application to pharmaceutical freeze-drying is developed.^ Augmented with computational fluid dynamics modeling, the simulation framework presented here allows to predict for the first time, dynamic product/process conditions taking into consideration specifics of equipment design. Moreover, by applying the modeling framework to process design based on a design-space approach, it has demonstrated that there is a viable alternative to empiricism.
Recommended Citation
Ganguly, Arnab, "Coupled fluid-thermal analysis of low-pressure sublimation and condensation with application to freeze-drying" (2014). Open Access Dissertations. 269.
https://docs.lib.purdue.edu/open_access_dissertations/269
Included in
Aerospace Engineering Commons, Mechanical Engineering Commons, Pharmacy and Pharmaceutical Sciences Commons