Supercritical fluids particle production

Kordikowski A, Shekunov T, York P. Crystallization of sulfathiazole pol5morphs using CO2. Proceedings of the 7th meeting on supercritical fluids. Particle design— Materials and natural products processing, Antibes/Juan-les-Pins, France, 2000. 

In 1994, we reported the dispersion polymerization of MM A in supercritical C02 [103]. This work represents the first successful dispersion polymerization of a lipophilic monomer in a supercritical fluid continuous phase. In these experiments, we took advantage of the amphiphilic nature of the homopolymer PFOA to effect the polymerization of MMA to high conversions (>90%) and high degrees of polymerization (> 3000) in supercritical C02. These polymerizations were conducted in C02 at 65 °C and 207 bar, and AIBN or a fluorinated derivative of AIBN were employed as the initiators. The results from the AIBN initiated polymerizations are shown in Table 3. The spherical polymer particles which resulted from these dispersion polymerizations were isolated by simply venting the C02 from the reaction mixture. Scanning electron microscopy showed that the product consisted of spheres in the pm size range with a narrow particle size distribution (see Fig. 7). In contrast, reactions which were performed in the absence of PFOA resulted in relatively low conversion and molar masses. Moreover, the polymer which resulted from these precipitation... 

In the RESS method, the solute of interest is solubilized in a supercritical fluid, which is then rapidly expanded through a nozzle. As the fluid expands, it loses its solvent capabilities and the solute precipitates out. While this technique has the advantage of not using any organic solvent, it is restricted by the generally poor solubility of most polymers in supercritical fluids. Indeed, polymers generally have to be below 10,000 MW in order to be eligible for this method of particle production [126]. 

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. 

The mixed-crystal system formed by indomethacin and saccharin (l,2-benzisothiazol-3(2H)-one-l,1-dioxide) has been used to evaluate the feasibility of using supercritical fluids as media for the design and preparation of new cocrystals [44]. In this work, the relative merits of supercritical fluid processes (i.e., cocrystallization with a supercritical solvent, supercritical fluid as anti-solvent, and the atomization and anti-solvent technique) were evaluated, as well as the influence of processing parameters on product formation and particle properties of the yields. It was reported that while the anti-solvent and atomization procedures yielded pure cocrystal products, only partial to no cocrystal formation took place when using the crystallization process. 

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. ... 

Micro- and Nano-particles Production Using Supercritical Fluids... 

Microemulsion polymerization in a supercritical fluid may provide some significant advantages compared with the same reaction in a conventional jiquid. Removal of the continuous phase following polymerization would certainly be faster and easier than removal following a similar reaction carried out in a conventional liquid. The ability to remove the continuous phase without the formation of a liquid-vapor meniscus and its accompanying strong surface forces could allow production of polymer with a very fine particle size. 

Precipitation from supercritical fluids is of interest not only in relation to the production of uniform particles. The thermodynamics of dilute mixtures in the vicinity of the solvent s critical point (more specifically, the phenomenon known as retrograde solubility, whereby solubility decreases with temperature near the solvent s critical point) has been cleverly exploited by Chlmowitz and coworkers (12-13) and later by Johnston et al. (14). These researchers implemented an elegant process based on retrograde solubility for the separation of physical solid mixtures which gives rise to high purity materials. 

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). 

Alessi P, Cortesi A, Kikic I, Foster NR, Macnaughton SJ, Colombo I. Particle production of steroid drugs using supercritical fluid processing. Ind Eng Chem Res 1996 35 4718-4726. 

---