Abstract: Simvastatin is a class of hydroxymethylglutaryl coenzyme A reductase inhibitors used to lower blood lipids and prevent atherosclerosis, but its poor water solubility and low bioavailability seriously affect clinical efficacy. In this experiment, simvastatin solid dispersions were prepared using supercritical CO₂ antisolvent method, and the prescription process parameters were optimized by Box-Benhnken response surface methodology, to improve the dissolution characteristics. The Box-Benhnken response surface methodology optimization experimental scheme took in vitro cumulative dissolution degree of simvastatin (dependent variable) as the evaluation index, investigated the influence of four factors (independent variables) including pressure, temperature, carrier type, and CO₂ outflow rate on the preparation of simvastatin solid dispersions by supercritical CO₂ antisolvent technology. Next, the particle size (PZ), infrared (IR) absorption spectrum, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) characterization were performed on the preferred process conditions for simvastatin dispersion. Based on these findings, further research was conducted on the in vitro dissolution properties of the product as well as the relative bioavailability after oral administration to rats. Animal experiments were approved by the Animal Ethics Committee of Jiangsu College of Food and Drug Engineering (No. JSSPYPCAC2024). The results showed that the optimal process parameters for preparing simvastatin solid dispersions by critical CO₂ antisolvent technology were pressure 12.00 Mpa, temperature 35.0 ℃, CO₂ flow rate 3.3 L·min^-1, F-127/PVP K23-27 (1∶10, w/w). The prepared solid dispersion was in a loose powder form, which appears as overlapping flaky aggregates under SEM. The laser particle size analysis showed a D50 value of 0.78 μm. DSC and XRD indicated that simvastatin existed in an amorphous form within the dispersion. The in vitro cumulative dissolution value after 60 minutes was 89.87%, and the relative bioavailability of oral administration to rats was 226.6%. In summary, this study successfully applied supercritical CO₂ antisolvent method to prepare simvastatin solid dispersions, simplified the experimental steps and optimized process routes using Box-Benhnken response surface methodology. The prepared simvastatin solid dispersions exhibited fast dissolution rates and high cumulative dissolution degrees, which can be used as a prescription strategy for developing novel oral simvastatin formulations with high bioavailability.