1. From laboratory- to pilot-scale: moisture monitoring in fluidized bed granulation by a novel microwave sensor using multivariate calibration approaches
- Author
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Jörg Breitkreutz, Wolfgang Taute, Claas Döscher, Michael Hoft, Robin Meier, Johanna Peters, and Reinhard Knöchel
- Subjects
Process analytical technology ,Pharmaceutical Science ,02 engineering and technology ,01 natural sciences ,Drug Discovery ,Process control ,Least-Squares Analysis ,Process engineering ,Microwaves ,Pharmacology ,Moisture ,business.industry ,Microwave sensor ,010401 analytical chemistry ,Organic Chemistry ,Pilot scale ,Resonance ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Fluidized bed ,Calibration ,Multivariate Analysis ,Environmental science ,0210 nano-technology ,business ,Fluidized bed granulation - Abstract
Recently, microwave resonance technology (MRT) sensor systems operating at four resonances instead of a single resonance frequency were established as a process analytical technology (PAT) tool for moisture monitoring. The additional resonance frequencies extend the technologies' possible application range in pharmaceutical production processes remarkably towards higher moisture contents. In the present study, a novel multi-resonance MRT sensor was installed in a bottom-tangential-spray fluidized bed granulator in order to provide a proof-of-concept of the recently introduced technology in industrial pilot-scale equipment. The mounting position within the granulator was optimized to allow faster measurements and thereby even tighter process control. As the amount of data provided by using novel MRT sensor systems has increased manifold by the additional resonance frequencies and the accelerated measurement rate, it permitted to investigate the benefit of more sophisticated evaluation methods instead of the simple linear regression which is used in established single-resonance systems. Therefore, models for moisture prediction based on multiple linear regression (MLR), principal component regression (PCR), and partial least squares regression (PLS) were built and assessed. Correlation was strong (all R
- Published
- 2018