The gas antisolvent (GAS) process has been employed for pharmaceutical micronization. Ampicillin was dissolved in organic solvent and carbon dioxide as an antisolvent was injected into this solution, consequently, volume expansion and sharp reduction in liquid solvent power were shown. The particles in GAS process are not seen in any operating conditions. Thermodynamic modeling of GAS can evaluate the operating conditions. In this project, the effect of solvent on optimal thermodynamic conditions of the binary system (CO2, solvent) and ternary system (CO2, solvent, ampicillin) were investigated. The relative change in molar volume in different solvent (ethanol, 1-propanol, 1-butanol, and 1-pentanol) was studied for determination of the optimum operating conditions. The combination of Peng-Robinson EOS and Vidal and Michelsen mixing rule (LCVM) was selected to determine the optimum operating condition of the GAS process. The effect of solvent on minimum pressure was investigated. The calculated Pmin was 70, 70.86, 72.2 and 73.4 bar for ethanol, 1-propanol, 1-butanol, and 1-pantanol at, 308.15 K respectively. According to modeling results, when the molecular weight of the solvent was increased, the value of Pmin was increased.