The control of high-shear wet granulation processes is one of the most difficult challenges in pharmaceutical processing. Granulation involves added a binder solution (often just water) to a powder mixture while undergoing high shear, and leads to many competing processes and constantly changing micro- and macro-environments within this highly dynamic system. Many different approaches have been attempted to model and control granulation, including power consumption/torque monitoring, NIR spectroscopy, and various attempts at physically monitoring granule growth (i.e. high-speed video microscopy, FBRM). Each of these methods has specific advantages and drawbacks but none has been shown to be clearly superior across variations both in equipment types and formulation variables.

Another method that has been used with some success is passive acoustic monitoring. One advantage to this approach in comparison to many of those mentioned previously is that the sensor attaches to the outside of the granulator, which eliminates problems that may arise from probe fouling. The system works by collecting sound data as the granulation proceeds, the theory being that as the granulator contents change over time (take up water/binder solution, grow in size, agglomerate, etc.) that the sound characteristics (both in terms of the intensity/loudness and the frequency distribution, or pitch) will alter in ways that reflect changes in the material within the granulation bowl. Sound capture covers frequencies that range from human hearing well into the ultrasonic region. Ongoing work has shown good reproducibility in terms of the evolving sound profile for a placebo mixture run in granulators ranging in size from 1 liter up to 10 liters and comparable responses that indicate good scale-up possibilities. Furthermore, granulations have been stopped and the contents analyzed to correlate changes both in size distribution and granule characteristics (porosity, tensile strength, etc.) to changes in the acoustic profile. The use of acoustics gives another means to investigate the change ongoing within high-shear granulation with an aim towards eventually developing more robust means of characterization and control.