Microparticles of theophylline were recrystallized using the high-pressure antisolvent technique. A mixture of ethanol and dichloromethane with a volumetric ratio of 1: 1 was used as solvents, and compressed CO, as antisolvent. The effects of process parameters (temperature, flow rate of solution and antisolvent, drying rate, initial solution concentration, diameter and length of the capillary expansion tube, and pressure gradient between the organic solution feed and the precipitation chamber) on particle size, size distribution and morphology were evaluated through an experimental design technique. In order to help selecting the appropriate operating conditions and understand the precipitation mechanism, the fluid phase behavior of ternary (CO2-solvents) and quaternary (CO2-solvents-theophylline) systems were investigated using a static synthetic method. Plate-like particles were produced in all experimental conditions with length ranging from 3 to 70 mu m. Also, slightly agglomerated particles were produced in some experiments, while in others a quite pronounced agglomeration was observed. Phase diagram of the mixture revealed that the contact mechanism between solution and antisolvent occurred in two different ways, influencing the aggregation, particle size and particle size distribution. The X-ray powder diffraction patterns (XRD) showed a change in theophylline crystallinity. This fact was confirmed by differential scanning calorimetry (DSC) analysis. Also, infrared spectroscopy analysis (FTIR) showed that the recrystallized powder presented a degree of purity higher than that of unprocessed theophylline. Thermal gravimetric analysis (TGA) indicated that the lower mass loss temperature values were found for small size particles and particles with crystalline structure. (c) 2007 Elsevier B.V. All rights reserved.