Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Engineering Science

Program

Chemical and Biochemical Engineering

Supervisor

Tribe, Lauren A.

Abstract

Powder mixing is a crucial and complex step in pharmaceutical production. Monitoring of mixing and segregation processes can be achieved using process analytical technologies to improve product quality. Passive acoustic emissions were examined during mixing in a V-blender. Vibrations from the emissions were measured through an accelerometer affixed to the outer V-shell arm lid. Horizontal and vertical loading configurations of particles were examined. Stable mixtures were reached when the measured amplitude plateaued around the approximate weighted average of the particles in the outer V-shell arm. Horizontal loading trials mixed faster and reached stable mixtures in fewer revolutions than vertical loading trials. Fill level can affect the mixing and segregation inside the V-blender. Passive acoustic emissions were further examined using different loading configurations and particle fill levels, supporting the effectiveness of this method for extracting information about mixing and segregation in pharmaceutical production to enhance product quality and manufacturing efficiency.

Summary for Lay Audience

Tablets and capsules are the most common dosage forms produced of all pharmaceuticals. During tablet and capsule production, several powders are mixed together until the needed uniformity is reached. Mixing is crucial during pharmaceutical production to prevent quality issues such as incorrect concentration of active constituent. Powder mixing must be monitored to ensure that products meet quality standards. Pharmaceutical industry currently uses monitoring methods that are expensive, invasive, destructive, and inefficient. Passive acoustic emissions are non-invasive, non-destructive method and offer effective monitoring of powder mixing at low cost.

Passive acoustic emissions were measured using an accelerometer attached to the lid of the outer arm of the V-shell. During powder mixing, segregation can develop and affect product quality. Segregation occurs when ingredients with different properties start to separate from each other. Different trials were completed to evaluate the effect of fill levels and different loading configurations of particles on mixing and segregation. One particle size was loaded into the V-shell on the bottom and the second particle size was loaded on top in case of horizontal loading and one particle size was loaded in the inner arm and the second one in the outer arm in case of vertical loading. Initially, the amplitude measured was similar to the particle loaded on top and in the outer arm. While mixing, the amplitude begins to change moving towards the amplitude of the particle loaded on the bottom and in the inner arm, before reaching a stable mixture and plateauing around the weighted average amplitude based on the relative fractions of the two particle sizes in the outer V-shell arm. The results showed that horizontal loading mixed faster and reached stable mixtures in fewer revolutions. The fill level trials showed that by increasing the fill level, the segregation decreased, and the mixing efficiency also decreased. The relationship between fill level and mixing efficiency, and segregation may not follow a straightforward pattern and results can be hard to analyze clearly.

Overall, this research helps support the potential for passive acoustic emissions to be used for monitoring powder mixing and segregation to improve final product quality.

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