To develop effective pharmaceutical formulations using supercritical carbon dioxide (scCO2) techniques, it is necessary to obtain the solubility of the medicinal ingredients in scCO2. In the current study, the solubility of Amantadine in scCO2 was evaluated under 28 different operating conditions involving seven pressures and four temperatures. To theoretically study this process, some popular empirical models and two well‐known thermodynamic models (PR‐WS and PC‐SAFT) were examined. The results suggest that the PR‐WS and PC‐SAFT models are the most accurate in establishing a correlation of the solubility of Amantadine in scCO2.