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Multiscale modeling and validation of particulate processes
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Sen, Maitraye. Multiscale modeling and validation of particulate processes. Retrieved from https://doi.org/doi:10.7282/T3TB18RJ

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TitleMultiscale modeling and validation of particulate processes
NameSen, Maitraye (author); Ramachandran, Rohit (chair); Glasser, Benjamin (internal member); Dutt, Meenakshi (internal member); Aglave, Ravindra (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2015
Other Date2015-05 (degree)
SubjectChemical and Biochemical Engineering, Pharmaceutical industry, Manufacturing, Pharmaceutical chemistry
Extent1 online resource (ix, 153 p. : ill.)
DescriptionSince solid handling and processing have a wide application in many chemical and pharmaceutical industries, it is important to understand the powder dynamics. The objective of this work is to build multiscale models (with the aid of different modeling techniques; PBM (population balance model), DEM (discrete element model) and CFD (computational fluid dynamics) for various solid/powder handling operations and design an integrated flowsheet model connecting the continuous API (active pharmaceutical ingredient) purification/processing and downstream tablet manufacturing operations (as applicable in case of pharmaceutical industries). At present there is no existing link between the API processing and purification and downstream tablet manufacturing operation. However it has been seen that the physical properties of API (size, shape etc.) have considerable effect on the critical quality attributes (CQAs) of the product obtained from the downstream tablet manufacturing operations. Therefore, such a flowsheet will allow a detailed study of the effect of upstream (API purification and processing) process parameters on the downstream (tablet manufacturing) product attributes. A multiscale modeling approach has been adapted in order to develop a novel PBM for powder mixing (an important unit operation in tablet manufacturing framework), which can track various CQAs such as RTD (residence time distribution), RSD (relative standard deviation) and composition of the final blended product. The model demonstrated good prediction when validated against experimental results. The mixing model has been used for developing a multiscale, continuous, integrated flowsheet model. In this flowsheet model, the mixing unit has been integrated with the API separation and purification steps (i.e. crystallization, filtration and drying). The crystallization model has been developed based on population balance methodology and experimentally validated. The flowsheet model has been further used to perform optimization studies and design an efficient hybrid MPC-PID control system. A multiscale CFD-DEM-PBM model has been developed for a fluid bed granulation process as well, which is an important operation present in the downstream tablet manufacturing framework (often present after the mixing operation). This model can be used to study the dynamics of the process and determine the CQAs of the granulated product. The multiscale model thus developed can be used to develop a reduced order model (ROM) which can be integrated with the flowsheet model. This work will make a significant contribution towards understanding the process dynamics, process design and optimization in order to enhance the efficiency of the pharmaceutical manufacturing processes.
NotePh.D.
NoteIncludes bibliographical references
Noteby Maitraye Sen
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3TB18RJ
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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