Effects of particle size and cohesive properties on mixing studied by non-contact NIR

A scaled-down convective blender was used along with non-invasive NIR spectrometry to study the mixing of citric acid, aspirin, aspartame or povidone with microcrystalline cellulose. NIR mixing profiles were generated in real time using measurements at the 2nd overtone wavelength of the added compounds. Trends demonstrated previously for aspirin were confirmed for additions of citric acid: the magnitude of the 2nd overtone NIR measurements is less affected by changes in particle size than that of the 1st overtone; the peak-to-peak noise of the 2nd overtone NIR mixing profile increases with the particle size of the added compound. The study has demonstrated the usefulness of continuous NIR measurements for rapid evaluation of the mixing process when deciding the best particle size of microcrystalline cellulose to mix with compounds of different particle shape and cohesive properties. Smaller particle sizes of microcrystalline cellulose (53–106 μm) were better for aspirin (212–250 μm), whereas larger particles (212–250 μm) were better for aspartame (212–250 μm). The characteristics of the compounds also need to be considered when deciding the order of addition of secondary compounds when mixed with microcrystalline cellulose. The time required to achieve a uniform mixture was much less when povidone was added before aspirin, rather than vice versa.