An experimental study of precipitation by CO2-antisolvent process has been performed with special attention to the role of phase behavior, spray regime and concentration in controlling morphology and dimensions of precipitates. Theophylline (THEO) was selected as model compound. Phase equilibria of solvent-CO2 and theophylline-solvent-CO2 systems were first investigated by a synthetic method, besides measurement of theophylline solubility in various solvents at atmospheric pressure. The solubility of theophylline in ethanol-CO2 (EtOH-CO2) and in ethanol-methylene chloride-CO2 (EtOH-DCM-CO2) mixtures was measured at 309.15 K and 10 MPa, based on the determination of the precipitation point. Besides confirmation of the antisolvent effect of CO2, the phase behavior study pointed the interest of an addition of methylene chloride to ethanol, since a significant enhancement of theophylline solubility was observed at atmospheric pressure and high pressure as well. Recrystallization of theophylline was successfully performed in a semi-continuous apparatus, provided that EtOH-DCM mixtures were used as dissolution media. The effect of pressure, temperature, theophylline concentration in the solution and solution flow rate were investigated. Plate-like aggregates were usually produced, with length ranging from 15 to 500 mu m depending on experimental conditions. Conditions of pressure and temperature were selected to explore both single-phase or two-phases conditions. Depending on those conditions, we observed two different mixing mechanisms that largely influenced size and aggregation of precipitated particles. Particularly, we have shown that conditions near the critical region led to a production of slightly aggregated particles below 15 mu m in length, with a precipitation yield of about 80%. (c) 2005 Elsevier B.V. All rights reserved.