Optimisation and Control of Dry Powder Mixing Processes Using a Mixing Sensitive Pigment

D Barling, D Morton, K Hapgood

A robust and novel method has been proposed to evaluate dry powder mixing using a mixing-sensitive colouring agent – sub-micronised iron oxide. The method measures the change in colour (hue) and hue intensity of blends over the duration of mixing and enables the analysis of two distinct mixing behaviours, namely pigment deagglomeration (transition from red to orange) and dispersion through the bulk material (increase in the intensity of the blend’s hue).
Several experimental campaigns were conducted with various inhalation grade lactoses, both free-flowing and cohesive, to observe whether blend pigmentation could serve as an indicator for mixing behaviour and phenomenon in different systems. Three mechanistically different blending technologies were predominant in the studies and blends were manufactured at a variety of operating conditions and scales. Through colourimetric analysis of each blend over time in different mixing conditions, a series of formulation specific process curves were generated based on the population of fine lactose particles and pigment. Process curves were found to be not only be able to quantify the level of pigment dispersion and de-agglomeration, but also analyse blend uniformity, energy input and detect the generation of fine particles through milling. These
results suggest that the iron oxide tracer method can be used as a simple and powerful preliminary approach to the optimisation of powder blending, and can potentially reduce both the cost and time traditionally associated with technology transfer or scale-up as it can show equivalent powder mixing between two systems or sets of mixing conditions.

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