Supercritical fluids crystallization

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... 

Supercritical fluid crystallization (SFC) is a technique for precipitating or crystallizing solutes dissolved in liquid solvents by injecting or mixing the solvent system with a compressed or supercritical fluid antisolvent. SFC is unique in that it uses a compressed gas to trigger the crystallization. Two benefits often associated with SFC include single-step processing of particulate pharmaceuticals with controlled... 

Other emerging crystallization techniques, such as supercritical fluid crystallization and sonocrystallization (ultrasound in crystallization), are also mentioned. Potential applications for these emerging technologies are present in the pharmaceutical industry. 

Velaga SP, Berger R, and CarlforsJ. Supercritical Fluids Crystallization of Budes-onide and Flunisolide. Pharm Res 2002, 19 1564—1571. 

Sievers RE, Hybertson B, Hansen B. European patent EP 0627910B1, 1993. Tavana A, Randolph AD. Manipulating solids CSD in a supercritical fluid crystallizer C02-benzoic acid. AIChE J 1989 35 1625-1630. 

Velaga SP, Berger R, Carlfors J. Supercritical fluids crystallization of budesonide and flunisolide. Pharm Res 2002 19 1564-1571. 

Other separation processes are liquid-solid extraction with supercritical fluids, crystallization, and separation by membranes. 

Hydrothermal crystallisation processes occur widely in nature and are responsible for the formation of many crystalline minerals. The most widely used commercial appHcation of hydrothermal crystallization is for the production of synthetic quartz (see Silica, synthetic quartz crystals). Piezoelectric quartz crystals weighing up to several pounds can be produced for use in electronic equipment. Hydrothermal crystallization takes place in near- or supercritical water solutions (see Supercritical fluids). Near and above the critical point of water, the viscosity (300-1400 mPa s(=cP) at 374°C) decreases significantly, allowing for relatively rapid diffusion and growth processes to occur. 

A crystalline or semicrystalline state in polymers can be induced by thermal changes from a melt or from a glass, by strain, by organic vapors, or by Hquid solvents (40). Polymer crystallization can also be induced by compressed (or supercritical) gases, such as CO2 (41). The plasticization of a polymer by CO2 can increase the polymer segmental motions so that crystallization is kinetically possible. Because the amount of gas (or fluid) sorbed into the polymer is a dkect function of the pressure, the rate and extent of crystallization may be controUed by controlling the supercritical fluid pressure. As a result of this abiHty to induce crystallization, a history effect may be introduced into polymers. This can be an important consideration for polymer processing and gas permeation membranes. 

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. 

Materials. Supercritical fluids offer many opportunities in materials processing, such as crystallization, recrystallization, comminution, fiber formation, blend formation, and microceUular (foam) formation. 

Gas AntisolventRecrystallizations. A limitation to the RESS process can be the low solubihty in the supercritical fluid. This is especially evident in polymer—supercritical fluid systems. In a novel process, sometimes termed gas antisolvent (GAS), a compressed fluid such as CO2 can be rapidly added to a solution of a crystalline soHd dissolved in an organic solvent (114). Carbon dioxide and most organic solvents exhibit full miscibility, whereas in this case the soHd solutes had limited solubihty in CO2. Thus, CO2 acts as an antisolvent to precipitate soHd crystals. Using C02 s adjustable solvent strength, the particle size and size distribution of final crystals may be finely controlled. Examples of GAS studies include the formation of monodisperse particles (<1 fiva) of a difficult-to-comminute explosive (114) recrystallization of -carotene and acetaminophen (86) salt nucleation and growth in supercritical water (115) and a study of the molecular thermodynamics of the GAS crystallization process (21). 

Supercriticalfluid solvents are those formed by operating a system above the critical conditions of the solvent. SolubiHties of many solutes ia such fluids often is much greater than those found for the same solutes but with the fluid at sub atmospheric conditions. Recently, there has been considerable iaterest ia usiag supercritical fluids as solvents ia the production of certain crystalline materials because of the special properties of the product crystals. Rapid expansion of a supercritical system rapidly reduces the solubiHty of a solute throughout the entire mixture. The resulting high supersaturation produces fine crystals of relatively uniform size. Moreover, the solvent poses no purification problems because it simply becomes a gas as the system conditions are reduced below critical. 

Crystallization Solutes may be crystallized from supercritical fluids by temperature and/or pressure changes, and by the PCA process described above. In the rapid expansion from supercritical solution (BESS) process, a SCR containing a dissolved solute is expanded through a nozzle or orifice in less than 1 ms to form small particles or fibers. A variety of inorganic crystals have been formed naturally and synthetically in SCR water. 

Depolymerization, e.g., polyethylene terephthalate and cellulose hydrolysis Hydrothermal oxidation of organic wastes in water Crystallization, particle formation, and coatings Antisolvent crystallization, rapid expansion from supercritical fluid solution (RESS)... 

Crystallization by reaction to form metals, semiconductors (e.g.. Si), and metal oxides including nanocrystals Supercritical fluid deposition... 

The advantages over conventional crystallization of crystallization under supercritical conditions are particularly clear, when non-volatile, thermally labile pharmaceutical substances are to be crystallized. As non-contaminating solvents at close-to-ambient temperatures, supercritical fluids might be an attractive alternative to conventional organic solvents. 

A high-pressure batch crystallization unit is presented in Figure 9.8-1. The substance is filled in a stirred autoclave, then the proper amount of supercritical fluid is pumped in, and the system is heated. When equilibrium is obtained, the temperature and/or pressure of the solution is varied until crystals are formed. 

Deryagin, B. M. Levi, S. M. Film Coating Theory, The Focal Press New York, 1964. Domingo, C. Berends, E. Van Rosmalen, G. M. Precipitation of Ultrafine Organic Crystals from the Rapid Expansion of Supercritical Solutions over a Capillary and a Frit Nozzle. J. Supercrit. Fluids, 1997, 10, 35-55. 

S. Rokushika, K. Naikwadi, et al., Liquid crystal stationary phases for gas chromatography and supercritical fluid chromatography, HRC CC J. High Res. Chromatogr. Chromatog. Commun., 5 480-484(1985). 

There is increasing interest in the crystallization of solutes from supercritical-fluid solvents. In such instances, solubilities often are correlated by an equation of state. Such concepts are beyond the scope of the current discussion but are presented elsewhere in the encyclopedia. 

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