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Predictive performance of loss-in-weight feeders for continuous powder-based manufacturing

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TitleInfo
Title
Predictive performance of loss-in-weight feeders for continuous powder-based manufacturing
Name (type = personal)
NamePart (type = family)
Li
NamePart (type = given)
Tianyi
NamePart (type = date)
1991-
DisplayForm
Tianyi Li
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Muzzio
NamePart (type = given)
Fernando
DisplayForm
Fernando Muzzio
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Glasser
NamePart (type = given)
Benjamin
DisplayForm
Benjamin Glasser
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Callegari
NamePart (type = given)
Gerardo
DisplayForm
Gerardo Callegari
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Oka
NamePart (type = given)
Sarang
DisplayForm
Sarang Oka
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
Genre (authority = ExL-Esploro)
ETD doctoral
OriginInfo
DateCreated (qualifier = exact); (encoding = w3cdtf); (keyDate = yes)
2020
DateOther (type = degree); (qualifier = exact); (encoding = w3cdtf)
2020-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2020
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
Continuous manufacturing for pharmaceutical solid dosage forms has reached a significant milestone over the past decade due to efforts from academia, industry, and regulatory agencies. Advancement in the development of equipment design, process analytical technology, control systems, and modeling tools has facilitated the growing interest in implementation of continuous manufacturing methods in major pharmaceutical companies around the world. The US Food and Drug Administration has also provided regulatory support for the implementation of continuous manufacturing using science- and risk-based approaches. As the pharmaceutical industry modernizes its manufacturing practices and implements more efficient and precise approaches, a more comprehensive evaluation of the process, including unit operations, is needed.

Loss-in-weight feeders, as the first unit operations in a continuous manufacturing design, are responsible for dispensing a given weight of material per unit of time to downstream unit operations accurately and constantly. Disturbances on a given feeder may travel downstream through the process and consequently impact critical quality attributes of the final products, such as potency and content uniformity. Therefore, it is essential to understand the potential aspects that could impact the feeder’s performance and how feeders and downstream unit operations would react in response to the different levels of disturbances and perturbations.

In this work, the effect on feeder performance in a direct compaction (DC) continuous manufacturing line was studied. Studies included the performance of feeders operating in normal gravimetric mode and the effects of feeder refills. Feeder tooling and material properties were both considered to determine their effect on feeder performance. Principal component analysis, a multivariate statistical analysis method, was utilized in order to build up a material library with 30 material flow properties. Partial least squares regression is used to correlate process performance to material flow properties. Multiple near infrared spectroscopy methods were applied to monitor the content uniformity exiting blend uniformity or content uniformity in the final product.

The results obtained from these studies were used to determine the design space for a commercially available loss-in-weight K-Tron KT20 feeder and its dependency on the conditioned bulk density of the powder. Additionally, a methodology was developed to correlate feed rate deviation caused by hopper refill to material flow properties and to create a predictive model.

To understand variations in drug concentration in a continuous direct compaction line, experiments were conducted on how perturbations on the mass flow rate from the feeders transfer down the continuous line, and how much dampening the downstream unit operations can provide to the variability in the mass flow rate. Controlled step changes in concentration and hopper refill operations were performed over short intervals with different blender speeds and total throughputs and the drug concentration in the blend and the tablets was characterized to determine residence time distribution and deviation in concentration.

The results from this work can be applied to the design of a continuous line, the development of a manufacturing plant, and the evaluation of process risks associated with the continuous manufacturing of solid dosage forms. Using the predictive methods enabled by the results discussed here, operators will be able to identify potential failure modes of the feeding operations and facilitate risk assessment for regulatory reporting.
Subject (authority = local)
Topic
Loss-in-weight feeders
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_11114
PhysicalDescription
Form (authority = gmd)
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 154 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-6tgx-8f63
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Li
GivenName
Tianyi
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-08-30 15:23:18
AssociatedEntity
Name
Tianyi Li
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2020-09-08T16:38:48
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