Nanoflakes of itraconazole, which is a poorly water-soluble antifungal drug, are produced using a procedure known as supercritical antisolvent solvent with enhanced mass transfer (SAS-EM). The nanoflakes show poor flowability and shelf life, each of which is improved by mixing with silica nanoparticles. To intimately mix at the nanoscale level, a macroscopic mixture of itraconazole nanoflakes and silica nanoparticles first is pressurized with supercritical carbon dioxide and then is rapidly depressurized through a nozzle. The rapid depressurization of the supercritical suspension (RDSS) causes deagglomeration and mixing, because of the high CO2 expansion velocity. Upon mixing, because of the presence of silica nanoparticles between itraconazole nanoflakes, growth of the drug particles during storage is avoided or reduced and the particle flow properties are improved significantly. The handling properties are characterized using properties such as the angle of repose, the compressibility index, and the Hausner ratio. Physical stability (shelf life) of the drug and drug/ silica mixture is tested by storing the samples for 25 days at 90 degrees C. Agglomeration and growth of pure drug nanoflakes during storage leads to a substantial decrease in the dissolution rate. However, when the drug nanoflakes are mixed with silica nanoparticles, the dissolution rate remains almost constant during storage. Thus, effective deagglomeration and nanoscale mixing lead to an increase in the shelf life.