Production of micro and nanoparticles of thermolabile compounds using supercritical assisted atomization

Abstract

Supercritical Assisted Atomization (SAA) is a very efficient process to micronize several kind of compounds, such as catalysts, polymers and active principles, also for pharmaceutical applications. The process is based on the solubilization of a controlled amount of CO2 in the liquid mixture, containing the compound to micronize, to reduce the cohesive forces, related to viscosity and surface tension, in order to obtain smaller particles than those could be obtained by process such as spray drying. The solution, formed by the liquid feed and supercritical CO2, is injected through a nozzle in a precipitation chamber where fast and complete evaporation of the solvent from the droplets takes place. The particles are collected on a porous filter located at the bottom of the precipitator. The SAA process has many applications in the micronization field, for this reason it is important to have a better comprehension of the principal mechanisms involved in the atomization process, to have a better control on particle size and distribution. For this reason the first part of this thesis work has been devoted to the evaluation of vapor liquid equilibria, involved in the saturator, and the fluid-dynamic of the jet break up. To evaluate the composition of the vapor-liquid phases, in the equilibrium conditions, a new approach, based on Raman Scattering, has been used. This technique, compared with the traditional used in thermodynamical studies, has the advantage to avoid any disturbance during the measurements. The systems aceton-CO2 and acetone-water-CO2 have been studied and the obtained compositions have been compared with results reported in literatures. The obtained results revealed that the vapor liquid equilibria detected by Raman are comparable with those obtained by other techniques. This part of the work was made in collaboration with SAOT institute in Erlangen (Germany). It is also important to understand the role of supercritical CO2 in the atomization process, from fluiddynamic point of view. For this reason Supercritical Dissolved Gas Atomization (SGDA) plant is used to analyze the spray by laser diffraction technique. The SGDA experiments were performed using two solvents: water and ethanol. Supercritical CO2 shows different behaviours with these solvents, since it is not soluble in water but it has a good affinity with ethanol. The laser diffraction analysis reveals that the droplet mean diameter strongly depends on gas to liquid ratio (GLR), since at low value of GLR (lower than 2) bigger droplets were obtained, whereas at GLR higher than 2, smaller droplets were obtained and no variation in droplet mean diameter was observed at higher value of GLR. Droplets obtained using ethanol are smaller than those obtained using water, this because the solubilization of supercritical CO2 in ethanol allows the decrease of cohesive forces due to viscosity and surface tension. Finally, the analysis of spray by laser diffraction lets to make hypothesis on the regime of atomization: this is bubbly for low value of GLR<1 and become annular for higher GLR. This because the amount of gas not dissolved in the liquid becomes considerably high and induces the nucleation of bubbles in the inner zone of the injector. Moreover, when GLR>1.5 the SMDs are considerably smaller than the diameter of the injector (2 order of magnitude), accordingly to the hypothesis of annular flow. On basis of the results obtained by the experiments on SGDA, a model compound was chosen for SAA micronization experiments, to enforce the theory previous discussed. Polyvinylpyrrolidone (PVP), that is a polymer that shows high affinity to polar solvents, was chosen as model compound. The solvents used were water, in which CO2 is not soluble, a water-acetone mixture, where acetone is a non-solvent for PVP and enhance the affinity of the liquid feed with supercritical CO2, and ethanol, that has a good affinity with CO2. The bigger particles (mean diameter ranged between 1.20 and 1.86 μm) were obtained using water as solvent, whereas using ethanol it was possible to produce the smallest particles (mean diameter ranged between 0.4 and 1.36 μm). Moreover, using ethanol as solvent, it was possible to change the operating conditions in the saturator in order to work in the one phase region of vapor liquid equilibria diagram. Keeping constant saturator temperature at 40°C, it was demonstrated that increasing saturator pressure (from 70 to 165 bar) smaller particles were obtained. When saturator pressure is higher than 100 bar, CO2 gives no contribution to a pneumatic effect, since, it is completely dissolved in the liquid. This fact could contribute to the demonstration that the main factor that influences the mean dimensions of the micro particles produced by SAA could be the amount of dissolved CO2; indeed, when SC-CO2 is completely solubilized in the liquid feed, smaller particles can be obtained... [edited by Author]