The present work investigates the formation of micro/nanoparticles by precipitation by pressure reduction of gas-expanded liquid (PPRGEL) using carbon dioxide (CO2). Rapid depressurization of the GEL solution results in very rapid evolution of CO2 bubbles and a concomitant large temperature drop (similar to 50-70 K). Consequently, the solid solubility is lowered, leading to heterogeneous nucleation at the CO2 bubble-GEL interface. A thermodynamic model based on the total entropy change of the depressurizing system is used for computing the time-variant reduction of the CO2 mole fraction in GEL for the CO2-acetone-cholesterol system. This, in turn, is used in a combination with a kinetic model for predicting the variation of nucleation rate and the resultant solute particle size. The model is used to analyze the effects of the pre-depressurization pressure and the depressurization time, the key process parameters, on the average particle size. The predicted particle size compares well with reported experimental data.