The micronization of a non-steroidal anti-inflammatory drug (NSAID), nabumetone, using the rapid expansion of supercritical solution (RESS) process was investigated in this study. Effects of the operation parameters for the RESS process were discussed by design of experiment (DOE) for the extraction temperature (T-ext), extraction pressure (P-ext), pre-expansion temperature (T-pre) and post-expansion temperature (T-post). Results from analysis of variance (ANOVA) showed that post-expansion temperature was the most significant factor, and a lower post-expansion temperature favored the production of smaller particles. In addition, the cross-interaction effect between the extraction pressure and post-expansion temperature was confirmed from the results of ANOVA. Further investigation on the micronization of nabumetone was demonstrated by changing the nozzle diameter (D-n) and spraying distance (L-s). The nabumetone particles were micronized from the original average size of 32.6 mu m to the smallest average size of 3.3 mu m through the RESS process in this study. This study reports the optimal operation conditions for the micronization of nabumetone. The micronized particles also show a much narrower particle size distribution. Measurements on the dissolution profiles for nabumetone before and after the RESS process were investigated. It is shown that the micronized nabumetone showed dissimilar dissolution behavior compared to the original compound. Its dissolution rate was enhanced by 3.5 times after the RESS process. (C) 2009 Elsevier B.V. All rights reserved.