Real-time monitoring of powder mixing in a convective blender using non-invasive reflectance NIR spectrometry.

A convective blender based on a scaled down version of a high shear mixer-granulator was used to produce binary mixtures of microcrystalline cellulose (Avicel) and aspirin, citric acid, aspartame or povidone. Spectra of stationary Avicel or aspirin powder provided an indication of the information depth achieved with the NIR spectrometer used in the study, and confirmed previously reported effects of particle size and wavenumber. However, it was demonstrated that for 10% w/w aspirin in Avicel, the information depth at the C-H second overtone of aspirin (about 2.4 mm) was unaffected by changes in the particle size of aspirin and was determined by the major component. By making non-invasive NIR measurements as powders were mixed, it was possible to illustrate differences in the mixing characteristics of aspirin, citric acid, aspartame or povidone with Avicel, which were related to differences in the cohesive properties of the particles. Mixing profiles based on second overtone signals were better for quantitative analysis than those derived from first overtone measurements. It was also demonstrated that the peak-to-peak noise of the mixing profile obtained from the second overtone of aspirin changed linearly with the particle size of aspirin added to Avicel. Hence, measurement of the mixing profile in real time with NIR spectrometry provided simultaneously the opportunity to study the dynamics of powder mixing, make quantitative measurements and monitor possible changes in particle size during blending.