Most pharmaceutical compounds are administered to the human body as tablets or by injection. If the dissolution of a drug is low, high dosage is needed and hence may cause some side effects to the human body. One method of enhancing the dissolution rate of a drug into the biological environment is to reduce the particle size. Cyclosporine A, one of the immunosuppressant drugs that have been commonly used for the treatment of respiratory tract infections, was chosen as the drug of interest since it has low solubility and high permeability (Class 2) in water. The phase behaviour of the cyclosporine-carbon dioxide (CO2) System was investigated prior to the micronization process. The melting point of cyclosporine substantially decreased from 150 degrees C at 1 bar to 25 degrees C at 55 bar when exposed to CO2 at high pressure. Micron-sized cyclosporine was successfully produced by both rapid expansion of supercritical solution (RES S) and particles from gas-saturated solution (PGSS) techniques. After micronization, the average particle size of cyclosporine precipitated by both techniques was found to be less than 1 mu m, which is related to a 97% reduction compared with the unprocessed cyclosporine. No significant change in the morphology and particle size was observed with respect to the extraction temperature and pre-expansion pressure, whilst an increase in nozzle diameter resulted in a slight increase in particle size and decrease in degree of aggregation. The fine particle mass (FPM) of micronized cyclosporine produced by RESS and PGSS was found to be 48 and 59%, respectively. (c) 2006 Elsevier B.V. All rights reserved.