Precipitation with a compressed antisolvent

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... 

Jarmer, D.J. Lengsfeld, C.S. Randolph, T.W. Manipulation of particle size distribution of poly(-lactic acid) nanoparticles with a jet-swirl nozzle during precipitation with a compressed antisolvent. J. Supercrit. Fluids 2003, 27 (3), 317-336. 

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

The organic-C02 interface plays a central role in physical particle formation processes including rapid expansion from supercritical solution (RESS), precipitation with a compressed antisolvent (PCA, also called SAS... 

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. 

Both the nucleation of supercritical anti-solvent bubbles in a polymer+organic solvent-rich phase in the supercritical anti-solvent process (SAS) (or, equivalently, precipitation with a compressed antisolvent PCA) (e.g., [76]) and the nucleation of bubbles of a dissolved supercritical fluid from a saturated and nozzle-expanded solution containing a solute to be precipitated, in the formation of particles from gas-saturated solutions (PGSS) [77] are bubble nucleation problems, to which the above ideas apply. In the latter case, the nucleation of bubbles occurs simultaneously with that of solid particles within the bulk supersaturated solution. 

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. 

Jarmer DJ, Lengsfeld CS, Randolph TW. 2006. Scale-up criteria for an injector with a confined mixing chamber during precipitation with a compressed fluid antisolvent. J. Supercritical Fluids 37 242-253. 

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). 

PRECIPITATION WITH A COMPRESSED FLUID ANTISOLVENT (PCA), A SUPERCRITICAL ANTISOLVENT (SAS), AND THE AEROSOL SOLVENT EXTRACTION SYSTEM (ASES) PROCESSES... 

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. 

Mawson S, Kanakia S, Johnston KP. Coaxial nozzle for control of particle morphology in precipitation with a compressed fluid antisolvent. J Appl Poly Sci 1997 64 2105-2118. 

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. 

Mawson S, Johnston KP, Betts DE, McClain JB, DeSimone JM. Stabilized polymer microparticles by precipitation with a compressed fluid antisolvent. I. Poly(fluoro acrylates). Macromolecules 1997 30, 71-77. 

Mawson S, Yates MZ, O Neill ML, Johnston KP. Stabilized pol5mer microparticles by precipitation with a compressed fluid antisolvent. 2. Poly(propylene oxide) and poly(butylene oxide)-based copolymers. Langmuir 1997 13 1519-1528. 

Gallagher PM, Coffey MP, Krukonis VJ, Klasutis N. Gas anti-solvent recrystallization new process to recrystallize compounds insoluble in supercritical fluids. In Johnston KP, Penniger JML, eds. Supercritical Fluid Science and Technology. Washington, DC American Chemical Society, 1989 334-354. Dixon D, Johnston KP, Bodmeier R. Polymeric materials formed by precipitation with a compressed fluid antisolvent. AIChE J 1993 39 127-136. Chattopadhyay P, Gupta RB. Production of griseofulvin nanoparticles using supercritical CO2 antisolvent with enhanced mass transfer. Int J Pharm 2001 228 19-31. 

Many volatile low-molecular-weight organics are completely miscible with carbon dioxide at relatively modest temperatures and pressures. However, nonvolatile compounds or those with higher molecular weights, especially polymers, are often insoluble. Insoluble liquid compounds may be dispersed into CO2 with the aid of appropriate surfactants to form a kinetically stable o/c emulsion [10,11]. Stable emulsions are important in separation processes, heterogeneous reactions and materials formation processes, such as precipitation with a compressed fluid antisolvent [40]. These emulsions are the precursors to solid latex particles in dispersion polymerization. Stabilization of o/c emulsions has been studied in-situ to understand surfactant design for polymerization [10,11]. 

Luna-Bdrcenas G., Kanakia S.K., Sanchez I.C., Johnston K.P., Semicrystalline microribrils and hollow fibres by precipitation with a compressed-fluid antisolvent, POLYMER, 1995, (36-16), 3173-3182... 

DIX Dixon, D.J. and Johnston, K.P., Formation of microporous polymer fibers and fibrils by precipitation with a compressed fluid antisolvent, J. Appl. Polym. Sci., 50, 1929, 1993. 

Mawson, S., Johnston, K. P., DeSimone, J. M., Betts, D. E. and McClain, J. B. (1997) Surfactant Stabilized Microparticles by Precipitation with a Compressed Fluid Antisolvent. 

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