DOI
https://doi.org/10.25772/1W3D-0K24
Author ORCID Identifier
0000-0001-6342-0860
Defense Date
2021
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Chemical and Life Science Engineering
First Advisor
Dr. Thomas Roper
Second Advisor
Dr. Frank Gupton
Third Advisor
Dr. James Ferri
Fourth Advisor
Dr. Hooman Tafreshi
Fifth Advisor
Dr. David Lai
Abstract
In recent decades within the pharmaceutical industry, an interest has grown in investing in flow chemistry and continuous manufacturing capabilities due to the possibility of increasing safety and mitigating risk, operating in novel processing windows of higher temperature and pressure, reducing the manufacturing footprint, and enabling a higher level of process and quality control. For low-throughput drugs, the target material generation rate can be readily obtained in continuous processes using relatively inexpensive equipment instead of unnecessarily large batch reactors. This can be beneficial both economically as well as strategically for flexible, on-demand production to mitigate drug shortages or supply chain disruptions. Process development strategies and results are presented across three distinct active pharmaceutical ingredient molecules on multiple projects, using various continuous manufacturing platforms. The optimization of the five telescoped ciprofloxacin synthesis steps and several manufacturing campaigns were carried out on the pharmacy on demand modules, and an online process modeling strategy was developed using flowrate and temperature readings coupled with kinetic data and a custom Python solver for the temperature and concentration equations. An automated platform for continuously stirred tank reactors with a highly corrosive reaction stream was developed to mitigate inherent scaleup concerns with the batch process. This generated hundreds of grams of pharmaceutical intermediate material with a continuous isolation unit operation after the reactor outlet. Computational fluid dynamics (CFD) models were developed for various tubular reactor systems to increase understanding on reactor design and performance. This knowledge was then applied to offer an elective course taught to graduate students where the governing equations and numerical methods were covered along with training in Python coding and the open-source computational fluid dynamics software OpenFOAM.
Rights
© Cameron T. Armstrong
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
11-22-2021