Interactions of phase equilibria, jet fluid dynamics and mass transfer during supercritical antisolvent micronization: The influence of solvents (original) (raw)
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Chemical Engineering Journal, 2010
Supercritical antisolvent (SAS) precipitation has been successfully used in the micronization of several compounds. Nevertheless, the role of high-pressure vapor-liquid equilibria, jet fluid dynamics and mass transfer in determining particle size and morphology is still debated. In this work, CO 2 has been adopted as supercritical antisolvent and elastic light has been used to acquire information on jet fluid dynamics using thin wall injectors for the investigation of the liquid solvents acetone and DMSO at operating conditions of 40 • C in the pressure range between 6 and 16 MPa. The results show that two-phase mixing after jet break-up is the phenomenon that characterizes the jet fluid dynamics at subcritical conditions. When SAS is performed at supercritical conditions a transition between multi-phase and single-phase mixing is observed by increasing the operating pressure. Single-phase mixing is due to the very fast disappearance of the interfacial tension between the liquid solvent and the fluid phase in the precipitator. The transition between these two phenomena depends on the operating pressure, but also on the viscosity and the surface tension of the solvent. Indeed, single-phase mixing has been observed for acetone very near the mixture critical point, whereas DMSO showed a progressive transition for pressures of about 12 MPa. In the second part of the work, a solute was added to DMSO to study the morphology of the microparticles formed during SAS precipitation at the different process conditions, to find a correlation between particle morphology and the observed jet. Expanded microparticles were obtained working at subcritical conditions; whereas spherical microparticles were obtained operating at supercritical conditions up to the pressure where the transition between multi-and single-phase mixing was observed. Nanoparticles were obtained operating far above the mixture critical pressure. The observed particle morphologies have been explained considering the interplay among high-pressure phase equilibria, fluid dynamics and mass transfer during the precipitation process.
The Journal of Supercritical Fluids, 2012
The context of the study is the Supercritical Antisolvent Process which required as a first step to investigate the disintegration of the injected solvent. In this paper, we focus on the simulation of the jet breakup in biphasic conditions, i.e. when the solution is injected into CO 2 under conditions below the mixture critical point where liquid and vapor phases coexist. Simulations are carried out under various conditions of pressure and solvent in order to modify significantly the properties known to influence the jet breakup such as density, viscosity and surface tension. Numerical results reveal that in the range of investigated Reynolds and Ohnesorge numbers, the classical criteria used to distinguish the different modes of jet breakup at atmospheric pressure seems to be valid for the high pressure environment, agreeing thus the experimental results reported in literature. Pressure effects are emphasized in this work and we show that simulations are able to represent that a modification of pressure allows for changing the jet breakup mode, especially near the mixture critical point. Furthermore, a relationship is proposed to estimate the jet breakup length as a function of the Weber number of the liquid phase.
Analysis of the mechanisms governing the supercritical antisolvent micronization
2003
Supercritical Antisolvent (SAS) precipitation is a semi-continuous precipitation technique developed to produce micrometric and sub-micrometric particles that are not attainable by conventional methods. Despite the fact that many works have been published on the generation of particles by SAS, only a limited number of them has been focused on the mechanisms controlling particle formation. In this work, a study of the precipitation process has been performed to understand the role of phase behavior in controlling morphology and dimension of the precipitates. The mixture Yttrium Acetate (YAc)/Dimethylsulfoxide (DMSO), using supercritical CO 2 as the antisolvent, has been chosen as the model system. The results showed that operating above the Mixture Critical Point (MCP) sub-micronic particles are generated nearly independently from the kind of the injector. We also demonstrated that it is also possible to obtain submicronic particles (with an average diameter of 0.28 µm) or macro-particles (up to 50 µm) by simply changing the operating pressure and/or temperature. These results have been explained on the basis of the position of the operating point with respect to the MCP of the pseudobinary mixture DMSO/CO 2. Particularly, we have seen that the single-phase region in the gasrich side of the pressure-composition solubility diagram and below the MCP can be usefully explored in order to modify the particle dimensions of the precipitate.
The Journal of Supercritical Fluids, 2011
An optical measurement technique, which is based on the Foerster resonant energy transfer (FRET) between two different dye molecules, has been applied successfully to observe volume expansion of a liquid solution, when it is pressurized with CO 2 . Rhodamine-B and Rhodamine-700 were dissolved in ethanol to form the FRET active dye solution. In a first "prove of principle" experiment, the sensitivity of the FRET efficiency towards volume expansion was demonstrated by pressurizing the liquid dye solution in a cuvette with CO 2 . From the rise of the meniscus of the solution inside the cuvette as a function of CO 2 pressure, the simultaneously acquired FRET spectra could be correlated with the volume expansion of the dye solution. In a second experiment, the dye solution was injected into CO 2 at different supercritical antisolvent operation pressures. FRET spectra were recorded 3 mm downstream of the injector nozzle, always upstream of the breakup of the injected liquid solution. At pressures below the thermodynamic mixture critical pressure (7.9 MPa @ 313 K) of the system ethanol/CO 2 no liquid phase volume expansion was observed. At pressures between the thermodynamic and the dynamic mixture critical pressure (8.5 MPa @ 313 K) of the same system, volume expansion could be evidenced before the breakup of the injected liquid solution.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2003
The hydrodynamic behavior of a solvent jet (ethanol) injected into a pressurized antisolvent (CO 2 ) fluid was experimentally investigated for a pressure range from far below to far above the critical point of the solvent-antisolvent mixture (CPM). The study shows that, at pressures sufficiently below the CPM, four traditional flow regimes (dripping flow, symmetric wave jet flow, sinuous jet flow, and atomization) can be identified depending upon the jet velocity and nozzle size. At pressures near the CPM where the equilibrium interfacial tension is extremely small (for pressure slightly below the CPM) or absent (for pressures above the CPM), all of these flow regimes can still be identified, indicating the existence of a dynamic interfacial tension (DIT). At pressures far above the CPM, only gas-like jets without any jet interfaces or droplet formation can be seen. The DIT near the CPM can be estimated from the measured stability curves (dependence of jet length on jet velocity) and our proposed analytic modeling. The zero-time DIT (ZTDIT) is insufficient to explain the jet behavior near the CPM since its relaxation time (microseconds) is very short in comparison with the jet breakup time (milliseconds). Hence another mode (or other modes) of DIT should exist. In this study, a new mode of DIT is proposed, namely, the nonisothermic DIT, which is caused by the enthalpy of mixing of two miscible fluids (such as solvent-antisolvent mixture near the CPM). The nonisothermic DIT enhances the jet stability for exothermic mixing while it reduces the jet stability for heat absorption, i.e. endothermic mixing. Both modes of DIT complement each other for jet stabilization. The ZTDIT stabilizes the small initial section of the jet while the nonisothermic DIT would stabilize (in case of exothermic mixing) the rest of the jet until its breakup.
Brazilian Journal of Chemical Engineering
The Supercritical Antisolvent (SAS) technique allows for the precipitation of drugs and biopolymers in nanometer size in a wide range of industrial applications, while guaranteeing the physical and chemical integrity of such materials. However, a suitable combination of operating parameters is needed for each type of solute. The knowledge of fluid dynamics behavior plays a key role in the search for such parameter combinations. This work presents a numerical study concerning the impact of operating temperature and pressure upon the physical properties and mixture dynamics within the SAS process, because in supercritical conditions the radius of the droplets formed exhibits great sensitivity to these variables. For the conditions analyzed, to account for the heat of mixture in the energy balance, subtle variations in the temperature fields were observed, with almost negligible pressure drop. From analyses of the intensity of segregation, there is an enhancement of the mixture on the molecular scale when the system is operated at higher pressure. This corroborates experimental observations from the literature, related to smaller diameters of particles under higher pressures. Hence, the model resulted in a versatile tool for selecting conditions that may promote a better control over the performance of the SAS process.
Mixing effects on particle formation in supercritical fluids
Chemical Engineering Research and Design, 2010
The process termed solution enhanced dispersion by supercritical fluids (SEDS TM ) is investigated. In the process particles are created in the rapid antisolvent process using a twin-fluid nozzle to co-introduce the SCF antisolvent and solution. Results of experimental and numerical studies are presented for two regions of pressure: above the mixture critical pressure where a single-phase exists for all solvent-antisolvent compositions, and below the mixture critical pressure where the two-phase region is observed. In experimental studies paracetamol (in the single-phase system) and nicotinic acid (in the two-phase system) were precipitated from ethanol solution using supercritical CO 2 as an antisolvent. To interpret the phenomena affecting creation of the supersaturation and to predict suprsaturation distribution, balances of momentum (flow), species (mixing), energy (heating and cooling) and population (droplet and crystal size distributions) are applied. The Favre averaged k-ε model of the CFD code FLUENT is applied together with specific models for precipitation subprocesses and Peng-Robinson equation of state. This includes application of the PDF closure procedure for precipitation and the drop breakage kernel that is based on multifractal theory of turbulence for modelling drop dispersion. Thermodynamic effects of mixing and decompression are included as well. Predicted values not always agree with experimental data but anyhow simulations predict all trends observed in experiments.
Chemical Engineering Transactions, 2015
Processes for precipitation of micro and nanoparticles using CO2 in supercritical state have proved to be an efficient way to process a large number of compounds from various fields, particularly in the pharmaceutical and food industry. In the face of experimental difficulties, the computer simulation appears as a useful tool to determine important parameters of the process. Using a three-dimensional mathematical model, it was studied the development of a jet of solution (ethanol and minocycline) expanded in pressurized carbon dioxide in order to interpret the process of development of regions of supersaturation of the solution. The commercial code ANSYS FLUENT was used to solve the model relating the impact of the flow of solution (1, 3 and 5 ml/min) in the mixing chamber of the precipitation process. The influence of turbulence in the flow dynamics was analyzed with the k-e and k-? models. Analysis of supersaturation profiles showed that by increasing the solution flow rate there ...
Powder Technology, 2005
A one-dimensional flow model has been proposed to describe the particle formation through the rapid expansion of supercritical solutions (RESS). This model includes the wall friction in the nozzle and heat exchange with the surrounding in the supersonic free jet region. The calculations were performed on the ibuprofen-supercritical CO 2 system in terms of the supersaturation, nucleation rate, critical nucleus size and number concentration of the critical nuclei. The results show that very high supersaturation (approximately 10 9), thus high nucleation rate, can be attained when the fluid leaves the nozzle exit to the supersonic free jet region. Simultaneously, the critical nucleus size, in the nanometer size, decreases, whereas the number concentration of critical nuclei increases. Besides, sensitivity analyses of pre-expansion pressures, pre-expansion temperatures and nozzle length have been carried out but found that they seem to not significantly influence the flow field properties.