Recrystallization from supercritical fluids

Of all the solvents considered in recent years as possible SCFs for crystallization processes, the only two that now command any notable attention are water and CO2 primarily because they are non-flammable, non-toxic, low-cost and readily available. Of these, CO2 is attracting greater support on account of its more accessible critical point (31 °C and 74 bar) compared with that of water (374 °C and 220 bar). 

Some recent examples of exploratory crystallizations using supercritical CO2 have been described by Mohamed, Debendetti and Prud homme (1989) Kelley and Chimowitz (1989) Sako, Satu and Yamane (1990) Berends, Bruinsma and van Rosmalen (1993) Liu and Nagahama (1996) Tai and Cheng (1997) Shekunov, Hanna and York (1999). 

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Micronization with supercritical fluids - Crystallization - Rapid expansion - Gas anti-solvent Recrystallization - Precipitation with compressed anti-solvent - Solution-enhanced dispersion - Particles from gas-saturated solutions 80 - 300 fine particles and powders from various products and of designed properties... 

The particle-size and size-distribution of solid materials produced in industrial processes are not usually those desired for subsequent use of these materials and, as a result comminution and recrystallization operations are carried out. Well known processes for particle size redistribution are crushing and grinding (which for some compounds are carried out at cryogenic temperatures), air micronization, sublimation, and recrystallization from solution. There are several practical problems associated with the above-mentioned processes. Some substances are unstable under conventional milling conditions, and in recrystallization processes the product is contaminated with solvent, and waste solvent streams are produced. Applying supercritical fluids may overcome the drawbacks of conventional processes. 

SCF technology has spread quickly from molecules such as naphthalene to more complex substances such as polymers, biomolecules, and surfactants. Supercritical fluids can be used to reduce the lower critical solution temperature of polymer solutions in order to remove polymers from liquid solvents(6.26 The technology has been extended to induce crystallization of other substances besides polymers from liquids, and has been named gas recrystallization(4). In other important applications, SCF carbon dioxide has been used to accomplish challenging fractionations of poly(ethylene glycols) selectively based on molecular weight as discussed in this symposium, and of other polymers(. ... 

The most important limitation of RESS is the low solubility of compounds in supercritical fluids and the use of co-solvent to improve solubility is usually costly and not economically feasible. As an alternative a supercritical fluid anti-solvent (SAS) process was introduced where a supercritical fluid is used to cause substrate precipitation or recrystallization from a polar liquid solvent (Subramaniam et ah, 1999). Zhong et ah (2008) successfully used SAS to produce alcohol soluble zein micro- and nanoparticles. A number of other technologies based on manipulating supercritical fluids have been successfully used to produce nanoparticles (Della Porta and Reverchon, 2008 Matsuyama et ah, 2003 Meziani and Sun, 2003 Shariah and Peters, 2003 Subramaniam et ah, 1999). 

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). 

The process acronym, GAS, describes how. supercritical fluids are employed in the process the gas is used as an antisolvent to precipitate a solute from a liquid solution. The process is generally applicable to the recrystallization of materials if two conditions are satisfied (1) if the compound is insoluble (or only slightly soluble) in the gas, and (2) if the gas is (very) soluble in the liquid. If a liquid solution containing the compound to be recrystallized is contacted with a gas, e.g., carbon dioxide, the gas will dissolve into the solution and, when sufficient gas is absorbed by the solution, the gas will act as an antisolvent and the material will recrystallize. 

Pharmaceutical Applications Since the residual solvent present in the extracted material is of crucial importance in the pharmaceutical industry, SC-CO2 has found several applications. The extraction of vitamin E from soybean oil and a purification method for vitamin E have been thoronghly studied. The latter process avoids the step of vacuum distillation, which usually results in thermal degradation of the product. Eavorable solubilities and recrystallization of various dmgs have been danon-strated in supercritical fluids. 

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