The effect of carrier particle size on the performance of adhesive mixtures for inhalation

Despite being subject to a multitude of investigations, the effect of carrier particle size on the performance of adhesive mixtures for inhalation is still not well understood. This study, involving three differently sized lactose carriers, all with the regular ‘tomahawk’ particle shape, aims to provide fundamental insight into this topic. Fine particle fraction (FPF) data for binary formulations with 2 % budesonide, blended both in the Diosna high shear mixer and in a Turbula blender, are analyzed in terms of the applied mixing force and mixing energy (ME). For high shear blended formulations, the results clearly indicate that the mixing force acting between adhesive units is directly proportional to the mass of the carrier particle. Formulations produced at different mixing times and speeds display a linear decrease in FPF when plotted against ME, with similar slopes for the different carriers, in particular as regard the relative decrease in FPF. The inhaler device affects the magnitude of the FPF, but not the relative decrease rate. Interestingly, formulations blended in the Turbula mixer show an opposite behavior, with increasing FPF at a longer mixing times/energies. This points to different mechanisms playing the key role in the two mixing regimes. In conclusion, the applied mixing energy, with carrier particle mass included in the equation, seems to play a crucial role for both mixers.