Interest in continuous pharmaceutical manufacturing (CPM) technology is rapidly growing, with all major pharmaceutical companies developing products in their pipelines using this technology. As it has been extensively reported, CPM can deliver enormous advantages including faster product development, less material use, reduced capital cost due to small equipment size, superior process control, optimized performance, and more reliable quality manufacturing. Nevertheless, given the novel and complex nature of the technology, CPM systems require further study compared to traditional batch processes. CPM studies must be carefully designed, optimized, validated, and controlled as holistic system in order to operate robustly, efficiently, and provide the aforementioned advantages. To achieve CPM’s advantages in full, it is necessary to develop and implement a framework wherein the processes can be evaluated and studied as integrated systems. In this work, tools established in the process systems engineering (PSE) methodology were implemented to develop models that can aid CPM process design, evaluation, control, and optimization. The focus of this work included the development and implementation of computationally efficient phenomenological and residence time distribution models for systems in a CPM system. In the first two chapters of this work, a thorough review of the current implementation of models in the pharmaceutical industry is presented. Within the review, the different types of models currently implemented in the industry are enumerated followed by the challenges of their implementation. Among some of the most difficult challenges for modeling CPM powder-based systems is the ability to determine relationships between critical process inputs and outputs, and the ability capture the impact of material properties on the process. To overcome these challenges a framework for developing predictive phenomenological (i.e., engineering) models that include the effect of material properties on the process was developed. The third and fourth chapters of this work are devoted to describing the model development framework and provide an example case study of the methodology when it was successfully applied to a tablet compaction process. The successful integration of material property effects into the modeling of the pharmaceutical unit operation led to the development of a material property library that collected a wide array of property measurements for a number of pharmaceutically relevant materials. The material property library, described in the fifth chapter of this work, was used as a tool to determine the impact of material properties on: (1) residence time distribution experiments and (2) the operation of continuous powder feeding units. Residence time distribution (RTD) methods and models were studied in this work, as their application to characterize CPM systems has become standard. The effect of material properties on RTD methods were evaluated in the sixth chapter to provide recommendations for using the RTD methodology to characterize CPM units. Ultimately, the unit operation characterization and modeling framework presented in this work along with the recommendations offered for RTD experimentation and modeling were applied to the development of a dynamic phenomenological and RTD model for a continuous powder feeding unit. The model, described in the seventh chapter of this work, was used to predict the behavior of the CPM-specific unit over a wide range of material property and process inputs.
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8933
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvi, 295 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Pharmaceutical technology
Note (type = statement of responsibility)
by Manuel Escotet Espinoza
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Embargo
DateTime (encoding = w3cdtf); (point = start)
2018-09-18
DateTime (encoding = w3cdtf); (point = end)
2020-05-31
Detail
Access to this PDF has been restricted at the author’s request. It will be publicly available after May 31, 2020.