All-trans retinoic acid (ATRA) is a derivative of retinol (or vitamin A) presenting similar benefits but considerable lower adverse toxicity, mainly in cases of high or long-term therapeutic doses. ATRA showed to be effective in the treatment and/or chemoprevention of several epithelial and hematological malignancies and diverse dermatological and eye diseases however, its low solubility in aqueous media and photosensitivity hinder its wider usage by the conventional administration methods. Supercritical fluids technologies are being widely used to enhance the in vivo bioactivity of this type of drugs both by improving their dissolution rate (using particle size reduction processes) and/or by controlling their release into the media after incorporation into solid polymeric/inorganic matrices (using supercritical impregnation/foaming processes). In both cases the solubility of the drug in the supercritical fluid (usually scCO(2)) is required for process optimization purposes. Therefore, in this work the solubility of ATRA in scCO(2) was measured at different isotherms (308.2, 318.2 and 328.2 K) and pressures that ranged from 10 up to 30 MPa using a static analytical method. Solubility data were correlated using three commonly used density-based models, namely the Bartle, Chrastil and Mendez-Santiago-Teja models. The solubility of ATRA in scCO(2) was found to be between 1.52 x 10(-6) and 1.84 x 10(-6) in terms of ATRA mole fraction and between 7.50 x 10(-3) and 1.07 x 10(-1) in terms of amount of solid solute per unit of volume of scCO(2). Fairly good correlation agreement was obtained with all the applied models being the lowest deviations obtained with the Chrastil model. ATRA particles obtained after scCO(2) processing (dissolution in scCO(2) followed by re-precipitation) were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) and in vitro dissolution studies. The results showed that the processed particles maintained their chemical structure and presented enhanced dissolution in aqueous media (PBS:ethanol, 80:20, v/v) when compared with commercial (non-processed) ATRA. (C) 2015 Elsevier B.V. All rights reserved.