Understanding the aerosolisation mechanism of carrier-based formulation with high drug loadings is crucial to developing high-dose dry powder inhalers. This paper investigated the effect of carrier-drug mass ratio in different conditions based on the combined computational fluid dynamics (CFD) and discrete element method (DEM) approach, aiming to develop better understanding of the aerosolisation mechanism of carrier-based formulation with high drug loadings. The carrier-based formulations composed of drug (salbutamol sulphate) and carrier (polystyrene bead) were formed with varied carrier-drug mass ratios ranging from 5:1 to 25:1. The aerosolisation process after impaction with a target wall was simulated and focuses mainly on the effects of four variables: carrier size, air flow velocities, impact velocities and impact angles. Dynamics of impact process and post-impact analysis were discussed. The fine particle fractions (FPFs), the amount of fine particles below 5 pm in the aerosol, were measured to characterise the aerosolisation performance. The results showed that increasing the carrier-drug mass ratio will improved the aerosolisation performance. The influencing degree of carrier-drug mass ratio on aerosol performance was dependent on the carrier size. For a larger carrier with a high carrier-drug ratio corresponding to high surface coverage, the airflow velocity, impact velocity and angle have only a minor effect on the aerosolisation performance. The best solution was to use the smaller carriers to replace the larger ones if the requirements of drug loading and FPFs need to be satisfied at the same time. These conclusions could be used to help design the optimal carrier-drug mass ratio formulations for different carrier-based dry powder inhaler systems. (C) 2016 Elsevier B.V. All rights reserved.