Production of nanoparticulate formulations by supercritical extraction of emulsions

MARÍA JOSÉ COCERO; ÁNGEL MARTÍN; FACUNDO MATTEA

Sendai

Congreso; Supergreen, international conference on supercritical fluid; 2009

The production of pharmaceuticals and food particles in the nanometer size presents clear advantages as the enhanced dissolution rates, the increasing suspension stability and solubility. The formulation of these compounds by encapsulation protects them against oxidation and allows its use as controlled delivery systems. A new promising technology to produce nanometer particles of natural substances is the use of supercritical fluids in combination with nanoemulsions, which presents advantages over these two separated technologies. This process, denominated Supercritical Fluid Extraction of Emulsions (SFEE), consists in extracting the organic solvent from the droplets of an oil-in water emulsion by using supercritical carbon dioxide. This extraction causes the precipitation of the solute. Each organic solvent drop behaves as a miniature Gas Anti Solvent precipitator, where the carbon dioxide diffuses through the aqueous phase to the drop, causing a considerable drop swelling. Depending operating pressure and carbon dioxide solubility in the aqueous and organic phases, the swelling caused by CO2 can be overcome by the diffusion of the organic solvent out the drop. The encapsulation of particles using SFEE to produce active compounds-polymer formulations can be achieved by dissolving the active solution in the disperse phase and the carrier in the continuous phase. This way, the emulsion provides a template for the final morphology of the microcapsules. Recently the application of the SFEE technology was used to form particles from different substances, for example the piroxam/PLGA, lysozyme/PLGA and β-carotene/ OSA starch. The polymers provide a double function as a surfactant for emulsion stabilization and as a coating material in the final product. The aim of this work is to present SFEE state of art, focusing on the fundamentals of the processes and the effect of operation variables. To describe the process a mathematical model of the mass transfer during the precipitation of β-carotene by emulsion spraying into supercritical carbon dioxide is presented. The model has been validated for the mass transfer to a single emulsion drop, which was studied by means of a microscopic camera, by the comparison of measured and calculated drop volume variation. Model results show that saturation of organic phase droplets with CO2 to produce anti solvent effect is fast and can take place during the drop fly time, but total removal of the organic solvent is slower and the experiments it was most probably completed by the extraction from the accumulated liquid in the precipitator.