Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Engineering Science

Program

Chemical and Biochemical Engineering

Supervisor

Briens, Lauren A

Abstract

Powder mixing is a critical and complex step of pharmaceutical production. Process analytical technologies can enhance the quality of a product through mechanisms including improved monitoring during mixing processes. Passive acoustic emissions were examined during mixing in a V-blender. Vibrations from the emissions were measured through an accelerometer attached to the lid of the outer V-shell arm. Analysis to extract information from the emissions was refined to obtain information about particle flow versus individual particle behavior. The initially measured amplitude in segregation-prone mixtures was like that of the particle loaded on top. A stable mixture was reached when the measured amplitude plateaued to the approximate weighted average of the particles in the outer V-shell arm. Overall, the passive acoustic emissions method was refined and extended to segregation-prone mixtures, supporting the effectiveness of passive acoustic emissions for extracting information about mixing in pharmaceutical production to improve product quality and manufacturing efficiency.

Summary for Lay Audience

Tablets and capsules are the most common forms in which pharmaceuticals are produced. In order to manufacture tablets, combinations of various powders must be uniformly mixed. When powders are incorrectly mixed there is a risk that the tablet produced may have quality issues, such as containing too much or too little of the active ingredient. To ensure that high-quality standards are maintained powder mixtures must be monitored. Current monitoring methods are invasive, expensive, and inefficient. Passive acoustic emissions have the potential to provide a non-invasive, low capital cost, and effective method of monitoring mixing.

Passive acoustic emissions were measured using a sensor attached to the lid of a V-blender. Different tests were completed to see how the measured amplitudes of the emissions were affected by factors such as impact location. These tests helped to improve the understanding of the particle motion during mixing in relation to the measured vibrations. This understanding helped to identify that when analyzing the data, using the top 50 highest amplitudes would give reliable, accurate information about the mixture.

In mixtures with multiple ingredients, segregation becomes a risk. Segregation occurs when ingredients with different properties begin to separate out from each other. To evaluate segregation, one particle size was loaded into the V-shell with the second particle size being loaded on top. Initially, the amplitude measured was similar to the particle loaded on top. During mixing, the amplitude would begin to change, moving towards the amplitude of the particle loaded on the bottom, before reaching a stable mixture and plateauing. The plateaued amplitude was noted to be representative of the weighted average amplitude based on the relative fractions of the two particle sizes in the V-shell arm.

Overall, this research helps to support the potential for passive acoustic emissions to be used for monitoring powder mixtures. By refining the data analysis methods, the extracted information about the process is more accurate and reliable. As well, being able to identify undesired mixture properties such as segregation will help to improve final mixture quality.

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