This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.

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Application of supercritical processing for co-precipitation of 5-FU and PLGA provided mild and non-aqueous conditions, so the hydrophilic drug incorporated in the polymer had good stability during the process.

The solubilities of flutamide, dutasteride, and finasteride in supercritical carbon dioxide were investigated at temperatures of (308.0, 318.0, 328.0, 338.0, and 348.0) K and various pressures in the range of (12.1 to 35.5) MPa. The measured results were then correlated using semiempirical equations presented by Chrastil and Bartle. With optimally fitted parameters, the average absolute relative deviations (AARD) ranged from 0.122 to 0.260 and from 0.024 to 0.137 for Chrastil and Bartle models, respectively. The heat of drug-CO 2 solvation and that of drug vaporization were approximated in the range of (-17.4 to -16.8) kJ • mol -1 and (73.7 to 90.1) kJ • mol -1 , respectively.