Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Engineering Science

Program

Chemical and Biochemical Engineering

Supervisor

Briens, Lauren

Abstract

Process analytical technologies can improve product monitoring and process efficiency in pharmaceutical manufacturing. Passive vibration measurements were evaluated for their potential as a technique to monitor lubricant dispersal in a V-blender. An accelerometer was attached to the lid of a V-blender shell to measure vibrations from particle collisions. Lubricants formed a layer around the surface of particles, altering energy dissipation upon impact. With mixing, vibrational amplitudes approached a stable value indicating a mixing end-point. Mixing profiles were sensitive to changes in particle type, particle size and distribution, and lubricant concentrations for ideal particles and pharmaceutical granules. Axial loading configurations provided better mixing performance compared to radial configurations. An optimal fill level for effective convective mixing was determined through vibration measurements. Overall, this research demonstrated the potential of using passive vibration measurements as a monitoring technique for lubricant dispersal in pharmaceutical manufacturing to improve control and efficiency of the mixing process.

Summary for Lay Audience

Prior to compression in tablet manufacturing, a lubricant is added and mixed in a V-blender to ensure the mixture is ejected from the tablet die smoothly. Mixing is conducted batch-wise and must be analyzed off line afterwards to ensure the mixture is uniform and will produce desired tablet properties, thereby a costly and time-consuming step within the manufacturing process. To improve process efficiency, inline monitoring methods using passive acoustic emissions or vibration measurements could be implemented. These methods are non-destructive, non-invasive, and have a reduced capital cost compared to other monitoring techniques.

An accelerometer was attached to the lid of a V-blender shell to measure vibrations from particle collisions. As particles tumbled, they impacted the lid of the V-shell transmitting a portion of energy into stress waves measured as vibrations by the sensor. When a lubricant was introduced, the lubricant formed a layer around the surface of particles, altering energy dissipation upon impact. With further mixing, the lubricant layer around the particles becomes more complete and uniform. Vibrational amplitudes then approached a stable value indicating a mixing end-point, allowing for the process to be monitored. Vibration measurements were sensitive to changes in particle type, particle size, and lubricant concentrations for ideal particles due to changes in momentum and energy transmission.

Vibration measurements were investigated to determine the effect of loading configuration and fill level on lubricant mixing performance. Axial loading lubricant configurations provided better mixing performance compared to radial configurations due to inherent V-blender mixing mechanisms. An optimal fill level for effective convective mixing was determined to be 21 – 23 vol %.

Lubricant dispersal for pharmaceutical granules was monitored using vibration measurements. Granules required a much smaller mixing time than ideal particles due to differences in particle surface morphology. Mixing profiles were sensitive to particle size, lubricant concentration, and segregation effects in both signal amplitude and variation. Overall, this research demonstrated the potential of using passive vibration measurements as a monitoring technique for lubricant dispersal in pharmaceutical manufacturing to improve control and efficiency of the mixing process.

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