To avoid the existing limitations of the PCA process for the precipitation of proteins and polar polymers a new approach based on the use of water to modify the phase behaviour of the system DMSO-CO2 was developed. The addition of water to the DMSO displaces the mixture critical pressure of the solution-CO2 system to higher pressures and produces a new operating region in which the PCA process can be carried out. Following this approach, it was possible to develop a process to produce 1-10 mu m particles of N-trimethylchitosan chloride (TMC) suitable for inhalation. Encapsulation of proteins in TMC using this technique could also be successfully achieved. (c) 2005 Elsevier B.V. All rights reserved.