Probing pharmaceutical powder blending uniformity with electrostatic charge measurements

The tribo-electrification of the powder particles is ubiquitous in pharmaceutical powder blending processes. It usually carries a negative connotation as particles may jam and stick inside equipments. Though it is practically important, the tribo-electrification is rarely characterized quantitatively in pharmaceutical areas. The purpose of this research was to examine the relationship between the electrostatic properties of pharmaceutical powders and blend homogeneity. We hypothesized that once the powder mixtures reached the homogeneity, the bulk electrostatic charges of the randomly collected samples at different spatial locations of the powder mixture would converge. Otherwise, the charges would scatter over a wide range due to non-uniformity of the powder mixture. Three prototypic pharmaceutical mixtures with (or without) caffeine as a model active pharmaceutical ingredient, microcrystalline cellulose as a filler/binder (Avicels), Cab-o-sil as a glidant, and Magnesium Stearate as a lubricant, were formulated and mixed in a V-blender. The resulted electrostatic charges were measured with a Faraday Cup connected to an electrometer and a strong correlation between electrostatic charges and blend homogeneity was found. The electrostatic charge monitoring method could be potentially used for assessing the blend uniformity. We also discovered the cyclical blending/deblending phenomena occurred with certain periodicity patterns upon continuous powder blending process, which may help design proper pharmaceutical blending procedures.