DOI
https://doi.org/10.25772/CB00-4655
Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Chemical and Life Science Engineering
First Advisor
James K. Ferri
Abstract
Continuous pharmaceutical manufacturing involves converting chemical reactants into active pharmaceutical ingredients via chemical transformation in interconnected vessels and flow reactors. These techniques and the associated advantages can be an essential strategy for reducing manufacturing costs and addressing shortages of lifesaving drugs, such as albuterol sulfate. Manufacturing of albuterol sulfate has historically only been performed in a batch operation mode, highlighting the opportunity to enhance the production approach to continuous. This work discusses the development of the primary reaction, an SN2 amination, in the continuous, end-to-end manufacturing of albuterol sulfate. Batch studies were conducted to observe process variable effects as well as determination of kinetic parameters. Laminar and plugged flow models were developed for predicting conversion of the starting material for both a first and second order reaction. Results showed optimal process conditions when the reaction was performed in isopropanol at 40°C, with an initial concentration of the limiting reagent to be 100 mg/ml. The laminar flow model for a second order reaction was most accurate at predicting conversion of the starting material in flow and indicated a necessary residence time of 30 minutes to achieve complete conversion. NMR was investigated as a potential process analytical technology for live reaction monitoring and process control. Key reaction species were identified and calibrated to enable quantification of amount present.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-9-2024