Investigation into the Effect of Humidity on Drug–Drug Interactions Using the Atomic Force Microscope

The atomic force microscope (AFM) has been used to characterize the cohesive nature of a micronized pharmaceutical powder used for inhalation therapy. Salbutamol sulfate (also referred to as albuterol sulfate), a therapeutic drug commonly delivered from dry powder inhalers (DPI), was chosen as a model system because the cohesion and subsequent de‐agglomeration during inhalation are critical aspects to the efficacy of such a delivery system. Salbutamol sulfate drug particulates were mounted on V‐shaped AFM cantilevers using a novel micromanipulation technique. Force–distance curves obtained from the measurements between cantilever drug probes and model compacts of salbutamol sulfate were integrated to determine separation energies. The effect of humidity (15–75% RH) on the energy required to separate a drug particle from model drug surface was determined using a custom‐built perfusion apparatus attached to the AFM. Separation energy measurements over 10 × 10‐μm areas of the compact surface (n = 4096) exhibited log normal distributions (apparent linear regression, R2 ≥ 0.97). Significant increases in the median separation energies (p