A method of rapid expansion of supercritical solutions into a liquid solvent (RESOLV) was used to precipitate and stabilize ultrafine particles of a poorly water soluble drug, Fenofibrate (FNB). In order to control particle size and its distribution (PSD), which are greatly affected by the inevitable growth and agglomeration, supercritical solutions of FNB prepared in SC CO2 at 100-200 bar and 333 K, were expanded in water with stabilizers using fine nozzles with diameters of 127-762 mu m and length varying between 3 and 6 cm. Stabilizers such as Tween 80, Sodium Dodecyl Sulfate (SOS), Pluronic F-68, Hydroxypropyl methyl cellulose (HPMC), and Sodium Alginate (SA) were used. Synergistic effect of SDS with polymeric stabilizers such as HPMC and Sodium Alginate was also examined. Co-precipitation of FNB with Poly (lactide-co-glycolide) (PLGA) was attempted to minimize particle growth and prevent agglomeration. Electrostatic stabilization compared to steric stabilization was found to be more effective in controlling PSD. FNB particles with sizes from 500 nm to 5 mu m could be precipitated with the use of different stabilizers. Overall, SDS was found to be a better stabilizer resulting in almost 66% particles less than 1 mu m, which remained stable after 24 h. Further, minor synergistic effects or PLGA co-precipitation or Sodium Alginate with SDS were observed. Finally, in order to increase practicality of this approach, multiple expansions of supercritical solutions of FNB in to a single collection sample were carried out to achieve higher particle concentrations of FNB in aqueous suspensions, albeit at the expense of increased particle size. However, even at high suspension concentration of 1.8 mg/mL, average particle size was under 3 mu m, and stable after 24 h, comparing very favorably with other approaches to produce FNB suspensions with high drug loading. (C) 2012 Elsevier B.V. All rights reserved.