| Summary: | During lyophilization, a freeze-drying process used to stabilize pharmaceuticals, vials filled with product go through stages to sublimate out the water contained in the initially frozen product. The final product is a solid with a low water content which is more stable for shipping. This work focused on a method for continuous inspection of product weight in vitro, specifically in the lyophilization context. Traditional batch lyophilizers cannot obtain continuous product weight data as a function of time during the lyophilization process on a vial specific basis (Laurens De Meyer, 2019). The weight-sensing approach developed presents an option for continuous or periodic interval collection of product weight data for the product in each vial. This method for continuous inspection of weight change of a product on a per vial basis allows for a much better understanding of the weight change over time and also opens up the possibility of altering process conditions to obtain a desired weight change over time profile for all vials.
In the larger lyophilization system for which this weight-measuring subsystem was designed the final product was required to be evaluated down to a 0.1% water content. There were additional system considerations such as viewing deflections, which could be related to weight changes, from the top of the system and strict limits on materials due to a need for sterility in the larger system. Largely as a result of these requirements a Keyence Laser Displacement Sensor was selected as the primary sensing method for deflection with an imaging/moiré approach as a secondary sensing method.
This thesis is focused on the options explored to measure product weight change through deflection of elastic structures used to support the vials during lyophilization. Ultimately, a Bent Spring wire approach was selected but this concept was heavily informed and inspired by Triangle Flexure and Diaphragm designs which were also explored but ultimately did not perform sufficiently given our strict deflection change requirement of at least 1mm. This 1mm deflection change threshold allows us to evaluate the final product down to a 0.1% water content. The performance of the deflection approaches and designs were experimentally tested by incrementally altering the weight supported by the designs. The experimental results were also compared with calculated results and simulation results. The Bent Spring design met the deflection change requirement as well as the other functional requirements and design parameters for the larger system. The Bent Spring approach is a method for measuring weight change of product continuously in each vial while also being simple to prototype and manufacture.
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