Drug particulate interactions in pressurized metered dose inhalers (pMDI) may lead to a decrease in aerosolization efficiency and subsequent efficacy in patient treatment. The interactions between salbutamol sulfate (commonly used in Ventolin pMDIs) and a series of pMDI canister materials were investigated using the atomic force microscope (AFM) colloid probe technique. Approximately 4000 individual force–distance curves were determined for a drug probe and three surfaces (10×10 μm areas) in situ, in a model propellant. The area under each force–distance curve was integrated to obtain separation energy values. Median separation energy values followed the rank order borosilicate glass > aluminum > PTFE, suggesting PTFE to be the most suitable canister coating.