In this study, an analytical dynamic method was optimized for small amounts of drugs and used to measure the solubility of cefuroxime axetil in supercritical CO2. After validating the experimental procedure with nimesulide, an active ingredient already studied in the literature, the solubility of cefuroxime axetil in supercritical CO2 was measured at temperatures varying from 308 to 328 K and pressures ranging between 8 and 25 MPa. Experimental values varied between 2.2 × 10-7 and 11.24 × 10-6 (in mole fraction) and a retrograde solubility behavior was observed. The solubility was correlated with semi-empirical density-based models: Kumar and Johnston, Mendez-Santiago and Teja, and Chrastil models. All three models successfully correlated the solubilities of cefuroxime axetil with an average deviation lower than 15 %.