|dc.description.abstract||This dissertation deals with the production of nanostructured organic, inorganic and biopolymer materials using supercritical carbon dioxide. Over the past decade, supercritical fluids (SCFs) have emerged for particle formation due to SCFs adjustable solubility and significantly high diffusivity. Various methods have been developed, which can be classified into two basic processes: (a) rapid expansion of supercritical solutions (RESS) for processing CO2-soluble materials, (b) and supercritical antisolvent (SAS) for processing CO2-insoluble materials. In this work, further developments in both the methods have been made to overcome the existing challenges and to achieve new nanostructures.
Chitin nanofibers are potentially of use in many biomedical and pharmaceutical applications. But, due to highly crystalline nature, it is very difficult to convert into a
nanofibrous form. In this work, a SAS method is used to produce chitin nanofibers of average diameter 84 nm using hexafluoroisopropanol as solvent while preserving the molecular structure of the processed chitin.
Using SAS with enhanced mass transfer, hydrocortisone nanoparticles were produced. A sonicating horn at 20 kHz frequency was used to enhance the mass transfer between solvent-antisolvent and to avoid agglomeration of nanoparticles. Particles as small as 180 nm are obtained using this method and the size was easily controlled using the ultrasound intensity.
The SAS process was further extended by including a chemical reaction. A new supercritical fluid based method, SAS-R was developed to form silica coating onto gold nanoparticles. Here supercritical CO2 is utilized both as an antisolvent and as a reactant. Silica-coated gold particles of 30-300 nm size were obtained with the coating thickness of as low as 20 nm. Pressure can be used to control coating thickness. Such particles are of interest in producing optical switches and biosensors.
In the conventional RESS process, a supercritical solution is rapidly expanded through a nozzle to precipitate the solute as microparticles. The modeling of RESS has shown that the precipitated particles at the nozzle tip are of the order of 5-25 nm in size. However, for most solutes, the final particles experimentally obtained are in the order of 800-3000 nm in size, due to growth by coagulation in the expansion chamber. Another difficulty is that most pharmaceutical compounds have poor solubility in supercritical carbon dioxide. In this work, both challenges are addressed by utilizing a cosolvent that is solid at the nozzle exit conditions. The solid cosolvent (SC) enhances the solubility and provides barrier for coagulation in the expansion chamber. The solid cosolvent is later remove from the solute particles by lyophilization (sublimation). The new process is termed as RESS-SC. A suitable solid cosolvent is menthol which is solid below 35 oC (typical nozzle exit temperature is 5-30 oC) and can be easily sublimed. RESS-SC concept is demonstrated by producing nanoparticles of griseofulvin, 2-aminobenzoic acid, phenytoin, and acetazolamide. A significant increase in the solubility and reduction in the particle size is observed in all four cases.||en_US