Drug solubility in compressed carbon dioxide is usually low, and for this reason, CO2 is not considered a suitable solvent. However, it can be used as antisolvent to crystallize a solute from a liquid solution. The choice of optimal pressure and the CO2/drug solution ratio is a crucial point of the process, and these values must be optimized. An estimation method based on the Peng-Robinson's equation of state is presented here with which to calculate the solubility of drugs such as Acetaminophen, Acyclovir, Atenolol, Carbamazepine, Ibuprofen, Naproxen, Nimesulide, and Sotalol hydrochloride in mixtures of CO2 and common organic solvents at a constant temperature but a variable pressure. The model temperature was 298 K for Ibuprofen and Naproxen, 315 K for Acetaminophen and 313 K for any other systems. This method is a practical and rapid alternative to experimental determination. (C) 2010 Elsevier B.V. All rights reserved.