Impact of blending parameters of the resonant acoustic mixer on the aerosol performance of ordered mixture formulations

Alex Wimbush¹, Kyrre Thalberg¹ & Hanna Persson²

¹AstraZenceca, Pepparedsleden 1, Mölndal, 431 50, Sweden

²AstraZeneca, Forskargatan 18, Södertälje, 151 85, Sweden

Summary

The Resonant Acoustic Mixer (RAM) can be used to formulate dry powder blends for inhalation. Due to the low shear forces involved, it shows particular potential for use with sensitive or fragile blend components. Understanding how the blending parameters impact on the fine particle performance of the resulting blends would have a significant benefit to the inhalation product development process.

The impact of acceleration and blend time was assessed for a range of lactose carrier grades of differing sizes and morphologies. This was initially carried out using coloured toner particles to visualise the blending process. This pre-work revealed that lactose carrier grades of small particle size required higher acceleration forces to promote efficient mixing.  It was also observed that there was a risk for a toner rich layer to form on the top of the powder bed, which could be overcome by increasing the acceleration.

The learnings from the pre-work were applied to set the parameters for a DoE, which encompassed the use of three carrier grades and two APIs. Statistical assessment of the results demonstrated that aerosol performance is influenced by both blend acceleration and time, with the fine particle performance reducing when increasing both factors. Isothermal calorimetry did not detect energy changes in the formulations, indicating that amorphous content has not been generated.

The study demonstrates that resonant acoustic mixing has the potential to influence the aerosol performance of formulations using the blend parameters, as well as the capability to formulate sensitive or fragile blend components.