The complexation of piroxicam and 2-hydroxypropyl-beta-cyclodextrin by means of supercritical CO2 has been investigated. The experiments were carried out by varying the temperature, pressure and contact time and introducing two different auxiliary agents: polyvinyl pyrrolidone or L-lysine. Cyclodextrins, which are widely used to solubilize a large variety of poorly soluble drugs, are often used in combination with some auxiliary agents to enhance the complexation efficiency of the conventional techniques. While many recent literature works report that supercritical carbon dioxide is a clean, nontoxic alternative to organic solvents, the use of auxiliary agents in the supercritical complexation process has been scarcely examined and still needs to be investigated. The inclusion complexes obtained in this work were analysed by means of the 'differential solubility method', differential scanning calorimetry and Fourier transform infrared spectroscopy. The results showed that the supercritical treatment could be successfully employed below 140-150 degrees C without incurring thermal degradation of the samples. While 66% inclusion efficiency could be obtained at 140 degrees C and 30 MPa for a mixture of piroxicam/2-hydroxypropyl-beta-cyclodextrin (1:2 molar ratio), higher percentages of complexation (95% in the ternary samples with polyvinyl pyrrolidone and 89-91% in those with L-lysine) could be obtained at a lower temperature (130 degrees C) when auxiliary agents were employed. (C) 2011 Elsevier B.V. All rights reserved.