Environmentally Benign Mixing of Nanoparticles

Abstract

Due to the increased use of nanocomposites, nanocatalysts, and nano-pharmaceuticals, mixing at nanoscale has become important. Conventional mixing techniques can be classified into: (a) dry mixing (mechanical mixing), (b) wet mixing, and (c) simultaneous production of mixed nanoparticles. Dry mixing is in general, not effective in achieving desired mixing at nanoscale, whereas wet mixing suffers from different disadvantages like nanomaterial of interest should be insoluble, has to wet the liquid, and involves additional steps of filtration and drying. This dissertation examines the use of environmentally friendly material, pressurized carbon dioxide, having high density and low viscosity to replace the liquids (e.g., n-hexane, toluene). Various techniques involving high pressure carbon dioxide have been developed for mixing of nanoparticles at the nanoscale. In the first method (Chapter 2), ultrasound is applied to the suspension of nanopowders in gaseous and supercritical carbon dioxide where high impact collisions during sonication help mixing and the final mixture is obtained by simple depressurization. Results show that mixing in carbon dioxide at higher ultrasound amplitudes is as good as in liquid n-hexane, and the final mixed product does not contain any residual media in contrast to the case of liquid n-hexane. In the second method (Chapter 3), which was specially applied to drug and excipient nanoparticles, a macroscopic mixture of drug nanoparticles and silica nanoparticles is first pressurized with supercritical carbon dioxide and then is rapidly depressurized through a nozzle. This method is termed as rapid depressurization of supercritical suspension (RDSS). Effective deagglomeration and nanoscale mixing is achieved using RDSS method leading to increase in the shelf life. In the third method (Chapter 4), applicability of sonication in liquid CO2 for mixing of drug (dipyridamole) and excipient nanoparticles is demonstrated for several binary mixtures of the drug and excipients. To intimately mix at nanoscale, macro mixtures of dipyridamole and excipient particles are sonicated in liquid carbon dioxide. Results of drug dissolution and blend homogeneity show effectiveness of the proposed mixing method for fine size particles. In fourth method (Chapter 5), microparticles of a poorly-water-soluble model drug, nevirapine (NEV) were prepared by supercritical antisolvent (SAS) method and simultaneously deposited on the surface of excipients in a single step to reduce drug-drug particle aggregation. In the method, termed supercritical antisolvent-drug excipient mixing (SAS-DEM), drug particles were precipitated in supercritical CO2 vessel containing excipient particles in suspended state. A highly ordered NEV-excipient mixture was produced. The produced drug/excipient mixture has a significantly faster dissolution rate as compared to SAS drug microparticles alone or when physically mixed with the excipients. Future work involves the testing the applicability SAS-DEM method and stirred mixing in liquid CO2 for mixing and deagglomeration of more variety of drug nanoparticles with various excipients.