The use of the supercritical fluid extraction of emulsion (SFEE) process for the polymer encapsulation of a low aqueous solubility drug substance was investigated, with focus placed on the carbon dioxide extraction step. The effects of process parameters-copolymer ratio, extraction time, pressure, and temperature-on the drug content, encapsulation efficiency, and drug release profile of the polymer-drug composite particle were studied. Ibuprofen and polylactic-glycolic acid were chosen as the model system. Encapsulated particles of 100-300 nm were successfully obtained after freeze-drying. XRD and SEM analyses confirmed the entrapment of ibuprofen in an amorphous polymer matrix and the absence of ibuprofen external to the encapsulated particles. In addition to the solubility of ibuprofen, the particle surface area and, to a small extent, the glass transition temperature were found to influence the drug content and drug release profiles. These understandings are expected to facilitate the rational design of the extraction step of the SFEE process, especially for drugs that are relatively soluble in supercritical carbon dioxide.