Abstract The solubility data of flufenamic acid (FFA, a fluorinated and non-steroidal anti-inflammatory drug) in supercritical carbon dioxide were measured with a semi-flow type phase equilibrium apparatus at temperatures from 313.2 K to 333.2 K and pressures up to 21 MPa. Over the experimental conditions, the solubility values are between 0.8 × 10−6 and 2.13 × 10−4 in mole fraction. These solid–gas equilibrium data were correlated with the Chrastil model, Mendez-Santiago and Teja model, and the Peng–Robinson equation of state to average absolute relative deviations of 11.4%, 21.1%, and 7.8%, respectively. Since the solubility of FFA can be as high as 10−4, rapid expansion of supercritical solution (RESS) method is favorable for preparing ultra-fine FFA particles. The experimental results of the RESS micronization show that extraction pressure, pre-expansion temperature, and dimension of capillary tube are the key factors to govern the morphology and the mean size of the resultant particles. While sticky agglomerates were obtained from lower extraction pressures with larger and/or longer capillary tube, needle-like particles were produced at higher extraction pressures with smaller and/or shorter capillary tube. Moreover, operating at lower pre-expansion temperatures and higher crystallization temperatures yielded longer and thinner needle-like crystals. Under higher extraction pressure (e.g., 21 MPa), the mean size of the generated FFA particles distributed from 0.5 to 5.1 µm and from 0.1 to 1.1 µm for the lengths of major and minor axes, respectively. It is also found that the particulate FFA converts from original form I into form III after the RESS processing.