TitleDesign, modeling and real-time monitoring of continuous powder mixing processes
NameVanarase, Aditya U. (author), Muzzio, Fernando J (chair), Glasser, Benjamin J (internal member), Ierapetritou, Marianthi G (internal member), Dave, Rajesh (outside member), Weinekötter, Ralf (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemical and Biochemical Engineering,
DescriptionContinuous processing is an advantageous alternative for the current methods used in the pharmaceutical manufacturing. Important advantages that it offers include smaller equipment footprint, reduced efforts in the scale-up work, and the potential to utilize already continuous processes to make the entire manufacturing more efficient. In the current pharmaceutical manufacturing environment, powder mixing process is carried out in the batch mode. The necessary methods and guidelines to design an equivalent continuous process are not well established. The work presented in this dissertation focuses on the characterization, design and optimization of a continuous powder mixing process for pharmaceutical powders. A systematic study was performed of the effects of process and design variables, and material properties involved in the continuous powder mixing process. The bulk powder flow behavior was characterized using the residence time distribution (RTD) measurement approach. Impeller speed, material bulk density and impeller design greatly influenced the mean residence time. With increasing impeller speed, mechanical fluidization was observed, which significantly affected axial dispersion coefficients. Intermediate rotation rates exerted maximum strain on the material, which leads to maximum homogenization. The strain measurements correlated well with the properties of tablets including content uniformity and tablet hardness. Mixing performance was largely dominated by the material properties of the mixture, and the blend uniformity measurement was affected by the sample size analyzed. An experimental protocol was developed to measure the blend uniformity in the in-line mode, and a methodology was further built to quantitatively relate the in-line NIR measurements with the off-line wet chemistry measurements. Considering the shear limitations of the continuous bladed mixer, alternative blending strategies, suitable for blending of cohesive materials were also demonstrated. A combination of a high-shear mixing followed by a low-shear mixing process provided the optimal mixing performance. The predictive understanding of the continuous powder mixing process developed in this dissertation can assist towards the design and development of a fully controlled continuous manufacturing process.
NoteIncludes bibliographical references
Noteby Aditya U. Vanarase
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.