Precipitation by compressed antisolvent

Solution-enhanced dispersion by supercritical fluids Precipitation by compressed antisolvent... 

Figure 3 (a) Schematic flow diagram of the solution-enhanced dispersion by supercritical fluids (SEDS) process, (b) Nozzle configurations of the SEDS and the precipitation by compressed antisolvent (PCA) processes. 

Falk, R. Randolph, T. Meyer, J. Kelly, R. Manning, M. Controlled release of ionic compounds from poly(L-lactide) microspheres produced by precipitation with compressed antisolvent. J. Control. Release 1997, 44, 77-85. 

As described in Chapter 3, several SCF techniques are available for the preparation of drug delivery systems. These include rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallization (GAS), supercritical antisolvent recrystallization (SAS), supercritical antisolvent with enhanced mass transfer (SAS-EM), solution-enhanced dispersion by supercritical fluids (SEDS), supercritical fluid nucleation (SFN), precipitation with compressed antisolvent (PCA), and aerosolized supercritical extraction of solvents (ASES). While RESS and SFN involve the expansion of a supercritical fluid solution of a drug to form drug particles, GAS, SAS, SAS-EM, SEDS, PCA, and ASES use a supercritical fluid as an antisolvent to precipitate particles of a drug dissolved in an organic solvent (5). General RESS and GAS processes are further elaborated in Sections 1.1.1 and 1.1.2. 

Abbreviations A, acetone ASES, aerosol solvent extraction system DM, dichloromethane DMF, A/,A/-dimethyl-formamide E, ethanol GAS, gas antisolvent process H, hexane HYAFF-11, hyaluronic acid benzylic ester I, isopropanol PAN, polyacrylonitrile PCA, precipitation with compressed antisolvent PCL, polycaprolactone PHB, poly(p-hydroxybutyric acid) PLA, polylactic acid PLGA, poly(lactic-co-glycolic acid) SAS, supercritical antisolvent process SEDS, solution enhanced dispersion by supercritical fluids TFE, 2,2,2-trifluoroethanol Triblock polymer, p poly(L-lactide-CO-D,L-lactide-co-glycolide)(62.5 1 2.5 25). 

Several processes utilizing supercritical fluids for materials processing have been reported in the literature although their commercial use is not well documented. Among the well-known processes are rapid expansion of supercritical solutions (RESS) (Phillips and Stella, 1993), the gas antisolvent process (GAS) (Yeo et al., 1993), aerosol solvent extraction system (ASES) (Bleich and Muller, 1996), a precipitation with compressed antisolvent process (PCA) (Brennecke, 1996), and solution-enhanced dispersion by supercritical fluids (SEDS) (Samp et al., 2000). The first four processes are for products that are soluble in the supercritical fluid or in an organic solvent. Biomolecules such as proteins or nucleic acids cannot be dissolved, and for such processes... 

PCA [Precipitation with a Compressed Antisolvent] A process for making a solid with unusual morphology by spraying a solution of it into a supercritical fluid. The process resembles spray drying into a supercritical fluid. Used for making microspheres, microporous fibers, and hollow... 

Table 3 lists different drugs precipitated by the SAS, ASES, and PCA processes. Almost all authors used carbon dioxide as the compressed antisolvent. 

Some examples of commercial active component production and production of substances with defined and uniform particle sizes (organic and inorganic materials) realized on pilot plant by using the RESS are given in Table 24.8. Other processes were also tested for synthesis of the particles with uniform size distribution as well as production of particles with specific structure (gas antisolvent recrystallization, GASR precipitation with a compressed antisolvent, PCA solution enhanced dispersion of solids, SEDS particles from gas-saturated solutions, PGSS) as shown in Table 24.9. All these processes are of special interest in pharmaceutical industry and in the production of different polymers. 

D.J. Dixon, K.P. Johnston, R. Bodmeier, Polymeric materials formed by precipitation with compressed fluid antisolvent, A/Ch 7,39(1), 127-139,1993. 

D. J. Dixon, "Formation of Polymeric Materials by Precipitation with a Compressed Fluid Antisolvent," Ph.D. Dissertation, University of Texas at Austin, Austin, Tex., 1992. 

Dixon, D. J., Johnston, K. P. and Bodmeier, R. A. AIChE Jl. 39 (1993) 127. Polymeric materials formed by precipitation with a compressed fluid antisolvent. 

Gas anti-solvent processes (GASR, gas anti-solvent recrystallization GASP, gas antisolvent precipitation SAS, supercritical anti-solvent fractionation PCA, precipitation with a compressed fluid anti-solvent SEDS, solution-enhanced dispersion of solids) differ in the way the contact between solution and anti-solvent is achieved. This may be by spraying the solution in a supercritical gas, spraying the gas into the liquid solution. 

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... 

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). 

When a solid has been solubilized in the liquid prior to the introduction of the compressed gas, the volumetric expansion is accompanied by a decrease of the liquid solvent strength, which causes the solid to precipitate as ultra fine particles. The physicochemical properties of the solute of interest strongly influence the choice of a solvent/antisolvent pair. The antisolvent should have appreciable mutual solubility with the solvent and should have little or no affinity for the solute. As will be seen, the solute-solvent affinity is also an effective factor that can strongly influence the morphology of the end product. 

Dozens of drugs have been recrystallized by means of the precipitation with a compressed fluid antisolvent (PCA) and the supercritical antisolvent (SAS) and aerosol solvent extraction system (ASES) processes. 

Magnan C, Badens E, Commenges N, Charbit G. Soy lecithin micronization by precipitation with a compressed fluid antisolvent—influence of process parameters. J Supercrit Fluids 2000 19 69-77. 

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