Supercritical antisolvent

Supercritical fluids can be used to induce phase separation. Addition of a light SCF to a polymer solvent solution was found to decrease the lower critical solution temperature for phase separation, in some cases by mote than 100°C (1,94). The potential to fractionate polyethylene (95) or accomplish a fractional crystallization (21), both induced by the addition of a supercritical antisolvent, has been proposed. In the latter technique, existence of a pressure eutectic ridge was described, similar to a temperature eutectic trough in a temperature-cooled crystallization. 

Shekunov, B. Yu., Baldyga, J. and York, P., 2001. Particle formation by mixing with supercritical antisolvent at high Reynolds numbers. Chemical Engineering Science, 56(7), 2421-2433. 

Nanoparticles of controllable size can be obtained in the supercritical antisolvent-enhanced mass-transfer (SAS-EM) process, which can... 

FIG. 20 22 Schematic of supercritical antisolvent with enhanced mass-transfer process to produce nanoparticles of controllable size. R, precipitation chamber SCF pump, supply of supercritical COg I, inline filter H, ultrasonic horn P, pump for drug solution G, pressure gauge. 

Reverchon, E. (1999) Supercritical antisolvent precipitation of micro- and nano-particles. Journal of Supercritical Fluids, 15 (1), 1-21. 

A number of techniques are based on supercritical fluid technology. Three are of particular pharmaceutical interest, namely the supercritical antisolvent (SAS) system, the rapid expansion of supercritical solution (RESS) method, and the gas antisolvent (GAS) technique [126]. 

Chapter Eight is concerned with a major question connected with the development of high pressure technologies in the process and chemical industry, i.e., the economic evaluation of production carried out at high pressures. In this case, also, the matter is discussed in relation to three important examples dense gas extraction, polymerization and supercritical antisolvent precipitation processes. 

The yield of drug precipitation in the collected particles is acceptable for drug Cx, as it can be seen in Table II. However, a problem arised when the drug used has a non-negligible solubility in the supercritical antisolvent in this case, the step for removing DMSO turned to be an extractive step for the drug already co-precipitated in the microspheres, as reported on Table II for Ex and Nx drugs. 

Chen C.-K., Duran M.A., Radosz M., Supercritical Antisolvent Fractionation of Polyethylene Simulated with Multistage Algorithm and SAFT Equation of State Staging Leads to High Selectivity Enhancements for Light Fractions, Ind. Eng. Chem. Res. 1994, 33(2), 306-10... 

Novel methods of preparation of vanadium phosphate catalysts have been explored by several groups these methods include hydrothermal synthesis, gas-phase s)mthesis, supercritical antisolvent precipitation, and the use of templates and structure-directing agents to modify the bulk... 

Hutchings and coworkers (78-83) pioneered the use of supercritical antisolvent precipitation to prepare a number of catalyst and support materials including vanadium phosphates. Vanadium phosphate precursor solutions were prepared from VOCI3 and H3PO4 refluxed in isopropanol. In the supercritical antisolvent precipitation method, a solution of the material to be precipitated and supercritical CO2 are pumped through a coaxial nozzle at temperatures and pressures above the critical point of... 

Hutchings and coworkers (78,149,150) prepared vanadium phosphate catalysts by using supercritical antisolvent precipitation. These materials were found to be amorphous by XRD and by electron diffraction, but they showed activity about twice as high as that of the standard vanadium phosphate catalysts. 

FIGURE 28 TEM and electron diffraction pattern (insert) of the vanadium phosphate catalyst prepared via supercritical antisolvent precipitation. 

Wang Y, Pfeffer R, Dave R. Polymer encapsulation of fine particles by a supercritical antisolvent process. 

Henczka, M. Baldyga, J. Shekunov, B.Y. Particle formation by turbulent mixing with supercritical antisolvent. Chem. Eng. Sci. 2005, 60 (8-9), 2193-2201. 

The supercritical fluid mefhod is a relafively new method, which can minimize the use of organic solvents and harsh manufacturing conditions taking advantage of two distinctive properties of supercritical fluids (i.e., high compressibility and liquid-like density). This method can be broadly divided into two parts rapid expansion of supercritical solutions (RESS), which utilizes the supercritical fluid (e.g., carbon dioxide) as a solvent for the polymer, " and supercritical antisolvent crystallization (SAS), using the fluid as an antisolvent that causes polymer precipitation. Recent reviews of the supercritical technology for particle production are available in the literature. ... 

SC CO2 exhibits weak solvent strength toward many organic and polymeric solutes. This antisolvent or non-solvent nature of SCFs can further be employed by spraying an organic solution of the drug and/or polymer through a nozzle into a compressed gas or SCF (Fig. 2C). This process, termed PCA, employs either a liquid or supercritical antisolvent. When a supercritical antisolvent is used, the process... 

Chattopadhyay, P. Gupta, R. Formation of protein micro-and nanoparticles using supercritical antisolvent with enhanced mass transfer. AIChE J. 2002, 48, 235-244. 

The supercritical antisolvent (SAS) precipitation has also been proposed in various arrangements and under various acronyms. This technique is based on the use of SC-CO2 as the antisolvent to precipitate the solid solute from a liquid solution. The prerequisites for the success of this technique are the complete solubility of the... 

At present, the most promising process seems to be the supercritical antisolvent precipitation, which is the most widely applied " and has been recently proposed on a semi-industrial scale. However, despite the fact that many works have been published on SAS precipitation, only a limited number of them have focused on the mechanisms controlling particle formation and on the role of the process parameters on the morphology and on the dimensions of the precipitated powders. This lack of information can be one of the main factors hampering the industrial application of this process. 

Thermodynamic constraints to the SAS process can be summarized in the required miscibility between the liquid solvent and the supercritical antisolvent and the insolubility of the solute in the antisolvent and in the solvent-antisolvent mixture. Data are available for various binary mixtures liquid-supercritical fluid and can be described as type I using the classification of van-Konynenburg and Scott. If jet break-up is obtained and mass transfer is very fast, high-pressure VLEs of the ternary system liquid-I-solute-I-supercritical fluid can control the precipitation process. 

Case e is the result of precipitation under conditions above the ternary MCP and is the true supercritical antisolvent precipitation. The formation of very small particles indicates that characteristic times for surface tension disappearance are very short, droplets are not formed at the exit of the injector and the very small particles are released from the fluid phase. These aspects have been studied in the previously cited works of Werling and Debenedetti," which underline the interplay among the different consecutive or simultaneous process that characterize SAS, mainly mass transfer under sub-critical and supercritical conditions. The characteristic times... 

Zhong, Q., Jin, M., Xiao, D., Tian, H., and Zhang, W. (2008). Application of supercritical antisolvent technologies for the synthesis of delivery systems of bioactive food components. Food Biophys. 3,186-190. 

Werling, J.O. Debenedetti, P.G. Numerical modeling of mass transfer in the supercritical antisolvent process miscible conditions. J. Supercrit. Fluids 2000, 18, 11-24. 

Gas antisolvent processes can be performed in a semicontinuous mode. In this case the solution and the antisolvent are continuously introduced in the system until the desired amount of the product is formed. The introduction of the solution is then stopped and the DG flux extracts the residual solvent from the system. The system is then depressurized to enable collection of the product. The solution is generally introduced through an atomization nozzle that favors the prompt expansion of the solution and the formation of small particles. Different process configurations have been utilized, i.e., co- and countercurrent introduction of the solution and antisolvent fluxes and various nozzles have been designed. The process is referred to by different acronyms such as ASES (aerosol solvent extraction system), SAS (supercritical antisolvent), SEDS (solution enhanced dispersion by supercritical fluids), PCA (precipitation with a compressed fluid antisolvent), GASR (gas antisolvent recrystallization), GASP (gas antisolvent precipitation). 

---