We have performed Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) simulations of air and particles in a commercial ELLIPTA® inhaler. We simulated the fluidization, deagglomeration and transport of carrier and API particles, with two realistic inhalation profiles that are representative of moderate asthma and very severe COPD patients, and three different mouthpiece designs. In each of the ten cases simulated, we determined the fine particle fraction (FPF) in the stream leaving the mouthpiece, the temporal evolution of the spatial distribution of the particles, the mean air (slip) velocity seen by the carrier particles, and the average numbers and normal impact velocities of carrier-carrier and carrier-wall collisions inside the inhaler. In the cases examined, the air-carrier and carrier-carrier interactions affected the FPF, while the carrier-wall interactions were too infrequent to have a substantial effect. The simulations revealed the benefit of loading both blisters even when only a single medication needs to be delivered.