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

Available for download on Saturday, November 21, 2026

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