(612d) A Novel Technique for Supersaturation and Particle Precipitation Measurements in High-Pressure Systems

There are several different supercritical fluid processes to produce tailor-made particles. Among them, the supercritical antisolvent process (SAS) is the most suitable process for the generation of amorphous nanoscaled particles. In the first step, a solution consisting of the solute and the solvent is prepared. This solution is injected into the previously pressurized carbon dioxide (CO2) which acts as an antisolvent on the solute. As the solute is completely soluble in the solvent and on the other hand nearly insoluble in the antisolvent CO2, a strong supersaturation due to the mixing process between the injected solution and the antisolvent is induced. To overcome this metastable supersaturated solution, nucleation and growth of the particles in the jet starts. Depending on the solute and the selected process conditions, different particle sizes and particle morphologies can be produced within the antisolvent precipitation process. For solutes which influence the quasi binary phase behaviour of the solvent/antisolvent system, as e.g. paracetamol, amorphous nanoparticles so far have not been obtained [1]. Several research groups investigated the solute paracetamol with the SAS process obtaining only crystalline microparticles [2-4]. At pressures far above the mixture critical point, nanoparticles precipitation is a matter of nucleation and growth from a gaseous supercritical phase [5]. Around the mixture critical pressure, microparticles ranging from 1 to 5 µm and hollow microspheres ranging between 10 - 30 µm are produced [6-8]. Several different research groups studied the SAS-process using different solutes and solvents and operated the process at different operation conditions. Based on this enormous effort, a lot of knowledge on different particle sizes and morphologies depending on the process parameters already exists. For the individual processes like the mixing process between solution and antisolvent, the obtained supersaturation and the nucleation and particle growth process, a lack of fundamental experimental work exists. In this work, an optical Raman and elastic light scattering setup was applied to the SAS-process, to visualize mixture formation between the solution and the antisolvent, and to obtain information on the existence of phase boundaries between the injected solution and the CO2. The phase boundaries arise either by means of the liquid solution or the solid particles which are precipitating. Thus, the measurement technique gives information on the mixture formation process, the location of particle precipitation and the phase state during precipitation [1, 9]. For the experiments, the solute Yttrium Acetate and the solvent Dimethylsulfoxide (DMSO) were used as a model system with well known particle characteristics investigated already [10]. With the same setup, but in contrary with just one camera for the elastic light scattering, equilibrium saturation concentrations for different pressures were measured. Applying this knowledge to the mole fraction distributions of CO2, measured via the concentration sensitive Raman measurement technique [1, 11], supersaturation profiles of the injected solution can be generated. For the measurements of the equilibrium saturation concentration, measurements in a high-pressure precipitation chamber at pressures between 8.5 MPa and 16 MPa were accomplished. Therefore, a solution consisting of the solute Yttrium Acetate and the solvent DMSO was mixed with carbon dioxide, which acted as an antisolvent, in a pre-mixing pipe at 313 K and the desired pressure and discharged into the high-pressure vessel trough a capillary nozzle with an inner diameter of 500 µm. The composition of solution and CO2 was equal in the pipe and the heated high-pressure chamber. By increasing the CO2 flow rate, the CO2 fraction was increased in small steps until the saturation concentration was reached and solid phase boundaries appeared. Since light is strongly scattered at the solid particles, the increase in elastically scattered light served as an indicator for reaching the saturation conditions. For the first time, an optical method was developed that revealed tremendous high supersaturations in supercritical precipitation processes. The results of this equilibrium saturation measurements show that even for very low solution concentrations nucleation appears if just a few droplets of CO2 are present in the mixture. As an example, for a solution concentration of 0.1 mg ml-1 Yttrium Acetate dissolved in DMSO, a CO2 mole fraction of 0.24 is enough to induce nucleation. The application of optical techniques is an important tool to understand the mechanisms governing particle formation, and therefore, to control their size and morphology. In-situ optical techniques are capable of following the very fast and dynamic individual steps during particle precipitation.

Acknowledgment: The authors gratefully acknowledge funding of parts of this work by the German National Science Foundation (DFG) and funding of the Erlangen Graduate School in Advanced Optical Technologies (SAOT) by the DFG in the framework of the excellence initiative.

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