Solvent-antisolvent method

Direct extraction of PHA from biomass (solvent - antisolvent methods PHA is a dissolved intermediary). 

An SCF can be used as an antisolvent, which will cause precipitation of a dissolved substrate from a liquid solvent. This approach, called the SAS (supercritical fluid antisolvent) or GAS (gas antisolvent) method, results in a pronounced volume expansion greater than with RESS, leading to supersaturation and then precipitation of the solutes. (Fig. 10). 

This attractive technique was first tested to micronize explosives (18,72-74). Mechanical methods such as milling generate high local temperatures, and therefore are useless in this particular case the use of SCCO2 as an antisolvent allowed comminution to proceed at mild temperatures. As already noted, the GAS process is a batch technique, which entails the gradual introduction of a compressed gas into a liquid solution of the solute of interest in a primary organic solvent. This method is based on the ability of liquids to... 

Non-halogenated solvent extraction (antisolvent method) Haloferax mediterranei Acetone Purity 98.4% recovery 91.4% [3]... 

MiCoS shares similar pros and cons to solvent-casting methods. With parallel preparation, it is highly efficient and effective in evaluating polymer types, drug loadings and antisolvent/solvent ratio comprehensively. However, the residue solvent and antisolvent content, which are critical for amorphous stability, cannot be determined due to low amount of solid products. The kinetic solubility results can only be interpreted qualitatively rather than quantitatively, as the particle size of the miniaturized products are not tightly controlled. 

Methods for isolation of the product polycarbonate remain trade secrets. Feasible methods for polymer isolation include antisolvent precipitation, removal of solvent in boiling water, spray drying, and melt devolatization using a wiped film evaporator. Regardless of the technique, the polymer must be isolated dry, to avoid hydrolysis, and essentially be devoid of methylene chloride. Most polycarbonate is extmded, at which point stabiUzers and colors may be added, and sold as pellets. 

A very important solvothermal method involves the use of supercritical C02 as an antisolvent that reduces the solvent strength, resulting in the precipitation of the oxide... 

SCFs have also been used in conjunction with organic solvents to generate particles of desirec morphology and attributes [56], One intrinsic limitation of SCFs is their inability to dissolve moderate to highly polar compounds. Such compounds can be easily dissolved in suitable organic solvents, and SCFs can be used as antisolvents to precipitate the solids. This procedure has been terme as solution-enhanced dispersion by supercritical Luids (SEDS). Depending on the method by which solution and SCF are introduced and mixed into each other, different applications have been described. These include ... 

The possibility to obtain a full solvent-free product, controlling in the same time the dimension of particles, is probably the most important feature when pharmaceutical substances are used. In the SAS process the SCF is used as the antisolvent. An organic solvent has to be involved in addition to the SCF and the solid solute. Basically, the process is performed by first dissolving the solid of interest in the organic liquid then, the SCF, which has low solvent capacity with respect to the solid but is completely miscible with the liquid, is added to the solution to get the precipitation of the solid. This method has been proposed by Gallagher and coworkers [8] to crystallize difficult-to-handle high explosives. Recently, other applications have been set forth to produce crystals of pharmaceuticals [9,10]. 

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. ... 

This issue, determining the point of seeding, is common to crystallization by cooling, as well as solvent removal by concentration, and by antisolvent addition. As such, seed point determination merits discussion of various methods. 

For solvent systems with a window of operating temperature, proper selection of the method of supersaturation generation (e.g., cooling and antisolvent addition) and mode of crystallization (e.g., batch vs. semicontinuous) can also affect the overall crystal growth rate. In many instances in which solvent or impurity rejection becomes critical, adequate mixing to avoid local high supersaturation can be critical. Examples 9-2 and 10-4 illustrate two cases of rejection of impurities and residual solvent. These examples show how various means are applied to overcome these complications. 

All of the above control factors are issues, as well as the local concentration gradients at the point of addition of the second solvent (also referred to as the antisolvent). This key point will be discussed in Chapter 9. Also discussed in that chapter is the method of seed introduction as a slurry with the antisolvent. This method can be useful in this case as well. 

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