One of the methods to reduce particle size is the GAS method. In this method, solute and antisolvent should be dissolved well in a solvent. But solute is not dissolved in a solvent. The aim of this modeling study is to determine the phase equilibrium and thermodynamic conditions of (CO2, solvent, 5-Fluorouracil) in the GAS process. The solvents include methanol, ethanol, acetone, 1-propanol, and 1-butanol. Peng-Robinson equation of state with a linear combination of Vidal and Michelsen mixing rules (PR-LCVM) was used for thermodynamic modeling. The volume expansion of the binary system (CO2, solvent) and ternary system (CO2, solvent, 5-Fluorouracil) at the temperature ranges of 313.15–319.15 K were investigated. The Pmin for the binary system was 66.7, 69.6, 60, 73.7, and 76.8 bar for methanol, ethanol, acetone, 1-propanol, and 1-butanol at 313.15 K, respectively. The Pmin for the ternary system was also calculated. The comparison between the binary and ternary system values showed that for a constant temperature and a certain solvent, the calculated minimum pressure in the ternary system was greater than in the binary system.