Author ORCID Identifier
https://orcid.org/0009-0001-1953-9415
Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Chemical and Life Science Engineering
First Advisor
Dr. 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. Due to purity requirements in the pharmaceutical industry, developing robust and reliable purification techniques is a significant area of interest regarding continuous manufacturing. This work discusses general drug salt purification steps within continuous manufacturing, including salt formation, crystallization, and an area of research that shows potential for use as a process intensification tool for continuous separations: tangential flow filtration (TFF). TFF is established in the pharmaceutical industry, but limited research exists for continuous separation of small molecule drug slurries. Experiments and design considerations for purification using TFF and distillation are explored as a basis for developing reusable pattern-based archetypes for separations processes. The use of commercially available, micro-filtration membranes as a multi-purpose unit operation for continuous drug salt processing and the design of a tailored distillation column are discussed within the context of a continuous albuterol sulfate manufacturing system. Results highlight solid removal, product concentration, and product washing applications of TFF leading to reduced filter-dryer cycle time and increased product throughput up to 30%. Distillation design was conducted utilizing experimentally determined equilibrium data and ASPEN+ software as a process development tool. The case-studies presented showcase TFF and distillation technologies as a continuous manufacturing tool to facilitate process intensification steps and continuously process API slurries in the pharmaceutical industry.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-9-2024
Included in
Catalysis and Reaction Engineering Commons, Membrane Science Commons, Process Control and Systems Commons