Drug excipient compatibility studies are considered important in successful formulation of drug products. Suggested methods for this purpose are thermal techniques under isothermal or nonisothermal conditions. In this study, modafinil, a wakefulness-promoting drug, was investigated under nonisothermal conditions using differential scanning calorimetry. Four different heating rates, 5, 10, 15, and 20°C/min, were performed for modafinil pure material and its physical mixtures with magnesium stearate (MgSt) or Gelucire 48/16. Activation energy (Ea) was calculated from the straight line of plotting a function of heating rate versus temperature and found that modafinil-Gelucire physical mixture increased Ea. This indicates drug-excipient interaction, supported by evidence from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. No significant interaction was detected with MgSt.