Pharmaceutical dry powder blending and scale-up: Maintaining equivalent mixing conditions using a coloured tracer powder

• Cost effective and simple method for industrial blend analysis
• Sub-micronised iron oxide used as a mixing sensitive colour tracer in lactose
• Colour change quantifies both tracer dispersion and de-agglomeration.
• Colour values in different blenders overlap to create formulation specific curves.
• Potential tool for scale-up, technology transfer and process optimisation

The identification and optimisation of operating conditions and selection of an appropriate mixer for the manufacturing of pharmaceutical dry powders is extremely challenging, and has relied largely on empirical trial-and-error approaches. A novel extension to a previous method has been proposed, which can be used to quickly and effectively evaluate the progression of a dry powder mixing using a mixing-sensitive coloured tracer powder. A series of lactose powders (white) with 1 wt.% sub-micronised iron oxide tracer (dark red) by weight were blended with three different mixing technologies under a range of processing conditions. Measurement of the hue and hue intensity of the powder blend as a function of time shows two distinct mixing behaviours: dispersion of tracer aggregates through the bulk powder (increase in blend hue intensity) and tracer de-agglomeration into primary particles (hue transition from red to orange). The colourimetric values of samples taken at blending times of up to 1 h were assembled to create a series of formulation-specific colour curves which were able to clearly distinguish and group mixers into low and high intensities given their range of values along the same formulation curves. This iron oxide tracer method provides the basis for a novel quantitative approach for ensuring equivalent blending conditions between mixer types, scales and operating conditions for a given formulation. The approach also shows the potential to identify conditions which may cause unintentional and undesirable particle attrition during powder blending.

Use of a mixing sensitive coloured tracer to determine dry powder mixing characteristics and aid in process optimisation and scale-up.Figure optionsDownload as PowerPoint slide