Surface modification of drugs for inhalation provides an approach to improve powder dispersibility and reduce intrinsic cohesion as micronised drugs tend to agglomerate. The intention of this study is to change interparticulate forces and improve the aerosolisation behaviour. The drug surface can be modified by using force control agents (FCAs). Mechanofusion systems use the applied mechanical forces for dry particle coating. In this study the picobond® system with AMS module was used to alter the surface of salbutamol sulphate (SBS) with different concentrations of the additive, magnesium stearate (Mgst). A design of experiments (DoE) was applied to evaluate the influencing parameters on the powder de-agglomeration which was investigated using a Next Generation Impactor (NGI). The fine particle fraction (FPF) (≤ 5 μm) was calculated and defined as response factor of the three factor central composite design (CCD) which is a standard response surface methodology (RSM). It was possible to find a significant model (p-value < 0.05) for the FPF. Furthermore, it could be shown that the rotational speed and the interaction between process time and Mgst concentration have a significant influence on the FPF. For higher excipient concentrations it is better to use a longer process time and vice versa. In this study the mechanofusion parameters are systematically investigated to obtain an improved process understanding.