Supercritical antisolvent processing methods

A supercritical fluid can be used as the external phase of a nanoprecipitation process. In this case, the method is named supercritical antisolvent processing" green tea polyphenols have been encapsulated in a biodegradable polylactide-PCL copolymer by a supercritical antisolvent process. ... 

The SAS methods have been used for preparing a variety of particles and fine powders from proteins, pharmaceuticals, pigments, polymers, and even explosives. For example, Debenedetti and coworkers used a continuous-flow, supercritical antisolvent process to prepare fine powders of trypsin, lysozyme, and insulin proteins (58-60). In the preparation a protein solution in dimethyl-sulfoxide (DMSO) was sprayed through a small orifice into supercritical CO2. The particles had diameters ranging from 1 to 5 p,m. The biological activity of the micrometer-sized powders was nearly the same as that of the starting materials. The method has also been used in the processing of pharmaceutically important compounds, such as salmeterol xinafoate (61), sulfathiazole (62), and methylprednisolone and hydrocortisone acetate (41). Kitamura et al. used the... 

Supercritical drying and particle formation processes are also important areas in SCCO2 based materials chemistry. Some of the particle processing methods available, such as precipitation with compressed antisolvent (PCA), are shown schematically in Chapter 9. 

A number of crystallization and precipitation techniques using SCFs have been considered, with special respect to the rapid expansion of a supercritical solution method (RESS) and to the SCF antisolvent processes (GASP). 

In the second method the solution is sprayed through a nozzle into compressed carbon dioxide the process is termed as precipitation with compressed antisolvent (PCA) [33] and liquid or supercritical antisolvents can be employed. In the case of continuous flow of the solution and of the antisolvent the process is termed also as aerosol solvent extraction system (ASES) [34], in the case of countercurrent flow and supercritical antisolvent precipitation (SAS) in the case of co-current flow [35]. 

A variety of methods have been reported for producing microspheres including phase separation by polymer/polymer incompatibility and coacerva-tion [81] solvent evaporation or solvent removal [82] hot-melt microencapsulation spray drying interfacial polymerization and supercritical fluidprocessing teehniques (such as the gas antisolvent spray precipitation process [83] or rapid expansion of supercritical fluids [84]). The characteristics of the most important of these methods have been reviewed [85, 86]. 

Supercritical anti-solvent and related processes (GAS/SAS/ASES/SEDS) In these processes, the SCE is used as an antisolvent that causes precipitation of the substrate(s) dissolved initially in a liquid solvent. This general concept consists of decreasing the solvent power of a polar liquid solvent in which the substrate is dissolved, by saturating it with carbon dioxide in supercritical conditions, causing the substrate precipitation or recrystallization. Depending on the desired solid morphology, various methods of implementation are available ... 

The bottom-up technique refers to synthesis based on atom-by-atom or molecule-by-molecule arrangement in a controlled manner, which is regulated by thermodynamic means (Keck et al. 2008). The process takes place through controlled chemical reactions, either gas or liquid phase, resulting in nucleatiOT and growth of nanoparticles. Bottom-up techniques (like supercritical fluid antisolvent techniques, precipitation methods etc.) create heavily clustered masses of particles that do not break up on reconstitution (Shrivastava 2008 Mishra et al. 2010). 

Another example in the literature on the preparation of pure polymorphic forms of drug compounds by SCF processing is that of fluticasone propionate, which is also a drug delivered by the respiratory route (27). As the compound decomposes before melting, DSC traces do not give definitive temperature profiles for the transformation between polymorphs I and II. X-ray diffraction patterns, however, have been used to confirm the presence of different polymorphic forms. The drug recrystallizes as form II from solution by the SEDS process in the presence of supercritical carbon dioxide at all temperatures, while form I is obtained by conventional crystallization methods. The rapid nucleation by SCF antisolvent aids in the formation of the metastable form II. A further advantage of SCF... 

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