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Building blocks of continuous pharmaceutical manufacturing

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TitleInfo
Title
Building blocks of continuous pharmaceutical manufacturing
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Keyvan
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Golshid
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Golshid Keyvan
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author
Name (type = personal)
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Muzzio
NamePart (type = given)
Fernando J
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Fernando J Muzzio
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Advisory Committee
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chair
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NamePart
Rutgers University
Role
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degree grantor
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NamePart
School of Graduate Studies
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school
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Text
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theses
Genre (authority = ExL-Esploro)
ETD doctoral
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2020
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2020-10
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2020
Language
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English
Abstract (type = abstract)
Continuous manufacturing (CM) is gaining popularity within the pharmaceutical industry as it is undergoing a shift from the conventional batch manufacturing of the last century to a new continuous paradigm that greatly enables use of advanced manufacturing methods. Continuous manufacturing offers many advantages such as flexibility, quality, robustness, higher yield, and lower manufacturing costs. Although CM is common in other industries (e.g., food and chemicals), it is an emerging technology in the pharmaceutical industry. Undoubtedly, continuous processing lends itself to in-process monitoring and closed-loop control. Process understanding, control strategies, and on-line, in-line, or at-line measurements of critical quality attributes provide for control strategies that include real- time quality evaluation of products. Under CM, real-time product quality assurance has been widely investigated under the Quality-by-Design (QbD) guidelines recommended by the FDA to advance the pathway to Real Time Release testing (RTRt).

Solid oral dosage products such as tablets and capsules constitute about 60% of global drug prescriptions, and their critical quality attributes (CQAs) such as hardness and dissolution, are well defined. Historically, they have been manufactured using batch methods and quality is evaluated by extracting a small number of samples that are subsequently subjected to destructive testing to evaluate quality. More recently, as the result of continuous processing, there is a movement away from end-of-line sample testing towards the adoption of in-process measurement strategies that ensure product quality in real-time. The first step in implementing an in-process test methodology towards RTRt is to identify the critical steps in the manufacturing processes, understand their failure modes, and develop design methodologies to prevent them from defeating the process.

In this work, we examined building blocks of two continuous manufacturing processes; DCCM (Direct Compression Continuous Manufacturing) and CHME (Continuous Hot Melt Extrusion). In both operations, we identified the critical processing parameters so that it could lead to implementing in-process testing methodologies that would enable RTRt. We characterized the process and examined the interplay between the process parameters and the product quality. This was accomplished by executing designed experiments on both processes and characterizing the tablets in terms of their critical quality attributes (CQAs) such as dissolution and hardness. Furthermore, we found a correlation between the tensile strength and dissolution of the continuously manufactured tablets and the processing parameters in the manufacturing line that can predict process performance. The predictive approach will not only enable us to develop a control strategy to determine the process parameters values that keep the process within the control space but also facilitate development of new solid oral dose products in the event of an emergency or drug shortages.
Subject (authority = local)
Topic
Continuous manufacturing
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
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Rutgers University Electronic Theses and Dissertations
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ETD_11255
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application/pdf
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text/xml
Extent
1 online resource (xii, 120 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-ejzc-hc54
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Keyvan
GivenName
Golshid
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-09-30 12:59:42
AssociatedEntity
Name
Golshid Keyvan
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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License
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Author Agreement License
Detail
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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Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2022-10-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2022.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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