Solubility of progesterone in supercritical carbon dioxide and its micronization through RESS

To investigate the formation of progesterone fine particles with rapid expansion of supercritical solution (RESS), it is vital to determine the solubility of progesterone under various equilibrium pressure and temperature conditions and to correlate the solubility data with a well-performed model. In this study, the solubility of progesterone in supercritical CO2 was measured using a dynamic apparatus at pressure ranging from 120 to 260 bar, and temperature from 313.15 to 338.15 k. The determined solubility in mole fraction is in the range of 5.3 Chi 10(-5)-8.9 Chi 10(-4) and correlated with three empirical density-based models and the Peng-Robinson equation of state model. The latter model has better correlation effects than the other density-based models and provides an overall average absolute relative deviation of 11.6% between the calculated and experimental solubility. Then, the performances of RESS under different conditions are evaluated by analyzing the particle characteristics, and the effects of extraction temperature, extraction pressure, and nozzle diameter on the particle size and particle size distribution of the formed particles are discussed. The original progesterone has a particle size of about 150 mu m while the average particle size of the micronized particles ranges from 0.11 to 3.22 mu m based on different experimental conditions. The particles were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared analysis (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and in vitro dissolution measurements. (C) 2014 Elsevier B.V. All rights reserved.