Monitoring quality attributes for high-shear wet granulation with audible acoustic emissions

Continuing development of process analytical technology (PAT) tools is needed in the pharmaceutical industry to provide more flexible processing and achieve products of consistent quality. For high-shear wet granulation, audible acoustic emissions (AAEs) have shown potential as a PAT tool for monitoring changes in physical properties related to product quality. This article develops the relationship between AAEs and two critical quality attributes, size and density, and investigates the potential for monitoring product quality online. Condenser microphones were placed inside the air exhaust of a PMA-10 high-shear granulator to collect AAEs for a design of experiment (DOE) where particle size and density were varied by changing the grade of Avicel in the formulation. The results showed increases in particle size and density affect the observed decreases in the AAEs at granulation end-point and during over wetting. In addition, the changes in size and density could be represented by different combinations of 10 Hz frequency groups and the trends in the multivariate scores support online monitoring.

Graphical abstractA design of experiment was used to vary particle size and density for a high-shear granulation process, by granulating with four different grades of Avicel. The results showed increases in size and density contribute to the decrease in audible acoustic emissions observed to coincide with granulation end-point and over wetting.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Granulation acoustics are affected by increases in particle size and density. ► Multivariate scores reflect changes in particle size distribution and density. ► Results support online monitoring of quality attributes using acoustics.