Non-invasive monitoring of the mixing of pharmaceutical powders by broadband acoustic emission.

Broadband acoustic transducers, including an intrinsically safe device, were assessed for non-invasive monitoring of aspirin, citric acid or Avicel mixing in a bench scale convective blender. The frequency information content of the acoustic emission (AE) spectra depends on the response characteristics of the transducers, which vary depending on the design. As acoustic waves generated from the impact of particles propagated through and around the glass mixing vessel, comparable spectra were obtained from different locations on the glass. The intensity of AE increased as the impeller speed, mass of powder or density of the particles was increased. AE also increased with particle size, with a relatively greater increase in intensity at lower frequencies. Mixing profiles were generated in real time from the change in the integrated intensity over selected frequency ranges on addition of aspirin to Avicel; the AE signal initially increased and then came to a plateau as the mixture became homogeneous. The average plateau signal was plotted against concentration for three different particle size ranges of aspirin in Avicel; for aspirin concentrations <21% m/m the increase in the AE was relatively small with no discernable effects of the aspirin particle size; however, for >21% m/m aspirin, there was a proportionally greater increase in AE, and particle size effects were more obvious. The study has shown that AE is relatively easy to measure non-invasively during powder mixing, but has poorer sensitivity than NIR spectrometry for detection of effects caused by addition of secondary compounds, especially at smaller particle sizes.