64. Sanganwar, Ganesh P.; Gupta, Ram B.. Enhancement of shelf life and handling properties of drug nanoparticles: nanoscale mixing of itraconazole with silica. Industrial & Engineering Chemistry Research (2008), 47(14), 4717-4725.
Nanoflakes of itraconazole, which is a poorly water-sol. antifungal drug, are produced by using a procedure known as supercrit. 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 mixt. of itraconazole nanoflakes and silica nanoparticles first is pressurized with supercrit. CO2 and then is rapidly depressurized through a nozzle. The rapid depressurization of the supercrit. 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. Phys. stability (shelf life) of the drug and drug/silica mixt. is tested by storing the samples for 25 days at 90. Agglomeration and growth of pure drug nanoflakes during storage leads to a substantial decrease in the dissoln. rate. However, when the drug nanoflakes are mixed with silica nanoparticles, the dissoln. rate remains almost const. during storage. Thus, effective deagglomeration and nanoscale mixing lead to an increase in the shelf life.