Ethosuximide is a succinimide anticonvulsant active pharmaceutical ingredient (API). It was used in our rapid expansion of supercritical solution (RESS) experiments with supercritical carbon dioxide as the solvent. Effects of four process parameters on the particle formation of ethosuximide were investigated. These parameters include the extraction pressure (P-ext), orifice nozzle diameter (D-n), pre-expansion temperature (T-pre) and post-expansion temperature (T-post). It is observed that an operation at a higher extraction pressure, lower post-expansion temperature and smaller orifice nozzle diameter is favorable for the production of smaller ethosuximide particles while the effect of pre-expansion temperature is insignificant. This API was micronized from its original mean size of 175.5 mu m to the smallest average size of 1.5 mu m at the optimal RESS process conditions. A polymorph conversion of ethosuximide was observed after the RESS process by physical properties characterization using the X-ray diffractometer (XRD) and differential scanning calorimetry (DSC). Measurements of the dissolution profiles for ethosuximide before and after the RESS process were also conducted. The micronized ethosuximide product shows novel dissolution behavior and significantly enhanced dissolution rate after the RESS treatment. (C) 2012 Elsevier B.V. All rights reserved.