Drugs with poor solubility in water, which indicates poor oral bioavailability, account for a considerable portion of new pharmaceutical candidates. Nanonization is a technique that overcomes this problem. However, current nanoionization methods have many disadvantages, including high energy demands, broad particle size distributions and the use of organic solvents. We report a new green method for preparing drug nano-particles by combining a subcritical water (SBCW) process with an anti-solvent precipitation method. The nano-particles processed through SBCW technology have a spherical morphology, a regular shape and a homogeneous particle size. Prednisolone nanoparticles averaging 31 nm in diameter were produced using this approach, and these particles were 10 times smaller size than the unprocessed drug. The resulting particle morphology depended strongly on operating conditions such as the temperature of the SBCW solution, the temperature of the anti-solvent and the concentration of the pharmaceutical excipients. Consequently, uniform prednisolone nanoparticles were produced through an environmentally friendly method. (C) 2014 Elsevier B.V. All rights reserved.