Abstract: OBJECTIVE To investigate the correlation between the thermo-rheological properties of the formulations and the hot melt extrusion(HME) process conditions for the preparation of solid dispersion. METHODS Arctigenin was adopted as the model drug, the carriers and drug-carrier mixtures were subjected to thermo-rheology study. Under certain stress and strain, the change of viscoelasticity with temperature was explored, thermo-rheological properties under shear frequency sweeping at a certain temperature was investigated too. The in vitro dissolution rate was employed as the index to investigate the formulation and processing parameters of HME with the results of scanning electron microscopy and X-ray diffraction to evaluate the effect of thermo-rheological properties on directing HME process conditions. RESULTS At the temperature 20 ℃ higher than the thermo-rheological glass transition temperature(Tgrheo), that was, Tgrheo+20 ℃, for all the formulations studied, the complex viscosity was <10⁴ Pa·s, which was the appropriate viscosity. Under the guidance of the results of thermo-rheological properties, the optimized formulation and process of arctigenin HME were obtained: HPMCAS-MG was used as the carrier, the arctigenin HPMCAS-MG ratio was 1︰6, the number of kneading blocks was none or a pair, the extrusion temperature was 155 ℃, and screw speed was at 30-70 r·min^-1. The solid dispersion obtained under these conditions enhanced the apparent solubility of arctigenin in the pH 6.8 buffer by nearly 13-fold. The dissolution rate reached 90% within 60 min, and the dissolution was stable within 3 h without precipitation. CONCLUSION The Tgrheo of formulation has important reference value for HME. Tgrheo+20 ℃ is suitable for HME and all the formulations studied in this experiment meet the rule. It is of great significance to improve the research efficiency of HME prescription optimization.