The effects of loaded carrier mass and formulation mass on aerosolization efficiency in dry powder inhaler devices

Previous studies have suggested that particle-particle impaction may influence aerosolization properties in carrier-based dry powder inhalers, through transfer of kinetic energy from large carriers to surface-deposited active drug. The importance of particle-particle collision has yet to be compared against other mechanisms that could lead to drug liberation, such as particle-wall impaction and turbulence. In particular, particle-particle collisions are difficult to model in silico due to computational restrictions. This study investigated the effects of dry powder inhaler particle-particle collisions in vitro using an established carrier-drug model dry powder inhalation formulation. Spherical polystyrene beads of median size 82.80 μm were chosen as a model carrier as they were of uniform size, shape, surface area, density, porosity and hardness and thus eliminated potential variables that would have conflicted with the study. This model carrier was geometrically blended with micronized salbutamol sulphate (loaded blend). The correlation between the mass of loaded blend (5-40 mg) in the Rotahaler® DPI device and resulting fine particle fraction (FPF) was examined at a constant flow rate of 60 L.min(-1). In a second experiment, the mass of loaded blend was kept constant and a variable amount of blank carrier particles were added to the Rotahaler® device to ascertain if additional "blank" carrier particles affected the final FPF. The efficiency of aerosolization remained constant with varying amounts of blank carrier particles as determined by the fine particle fraction of the emitted dose (FPFED) and fine particle fraction of the loaded dose (FPFLD). No statistical difference in FPFED and FPFLD values were observed for increasing masses of blank carrier. In addition, no statistical difference in FPFED and FPFLD between the two experiments was obtained. These observations suggest that particle-particle collisions are not a driving mechanism responsible for deaggregation of drug from carrier-based systems.