Investigation of continuous wet granulation processes via implementation of pharmaceutical quality by design principles
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Meng, Wei.
Investigation of continuous wet granulation processes via implementation of pharmaceutical quality by design principles. Retrieved from
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TitleInvestigation of continuous wet granulation processes via implementation of pharmaceutical quality by design principles
Date Created2018
Other Date2018-05 (degree)
Extent1 online resource (xxvii, 255 p. : ill.)
DescriptionWet granulation is a widely used downstream unit operation for size enlargement in the manufacturing of solid oral dosage forms. It has also been considered as a particle design technique to improve powder flow properties, reduce ingredient segregation and modulate compatibility of particulates as well as drug release kinetics. In recent years, continuous manufacturing has been drawing considerable attention due to its intrinsic advantages over conventional batch processing such as improved manufacturing efficiency and enhanced product quality. The main focus of this dissertation is to understand diverse continuous wet granulation systems by employing pharmaceutical quality by design principles. The performance of different commercial twin-screw and high-shear granulators were compared and their design space was explored by leveraging statistical design of experiments. Critical process parameters (e.g., rotation speed, liquid to solid ratio, throughput and barrel temperature), design elements (e.g., screw configuration and injection location of liquid constituents) and formulation variables (e.g., drug hydrophobicity, primary particle size, binder delivery methods and granulation liquid viscosity and surface tension) were comprehensively studied to examine the influence on critical attributes of granules (e.g., size distribution, porosity, bulk density, tapped density, flowability, strength, drug segregation and particle shape) and tablets (tensile strength, porosity, friability, disintegration time, drug agglomerate size distribution and release kinetics). Furthermore, process understanding was enhanced by unraveling the granulation mechanisms with fundamental regime maps regarding wetting and nucleation as well as consolidation and coalescence. Dissolution mechanisms of tablets produced at different processing conditions were elucidated by delving into the discrepancy in their physical and chemical microstructures. In addition, several complementary process analytical technologies such as EyeconTM, near-infrared and Raman spectroscopy were implemented in a twin-screw granulation process to enable real-time release testing of granule physical properties and drug content uniformity.
NotePh.D.
NoteIncludes bibliographical references
Noteby Wei Meng
Genretheses, ETD doctoral
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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