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Particle generation for pharmaceutical applications using supercritical fluid technology

Abstract : in the pharmaceutical industry, an even greater number of products are in the form of particulate solids. Their formation, formulation and the control of their user properties are still not well understood and mastered. Since the mid‐1980s, a new method of powder generation has appeared involving crystallisation with supercritical fluids. Carbon dioxide is the most widely used solvent and its innocuity and ``green'' characteristics make it the best candidate for the pharmaceutical industry. Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti Solvent (SAS) and Particles from Gas Saturated Solutions (PGSS) are three families of processes which lead to the production of fine and monodisperse powders, including the possibility of controlling crystal polymorphism. For the RESS process, the sudden decompression of the fluid in which a solute has been dissolved is the driving force of nucleation. CO2 is, however, a rather feeble solvent and this is obviously the main limitation of the development of RESS. In the SAS process, CO2 acts as a non‐solvent for inducing the crystallisation of a solute from an organic solution. The versatility of SAS (there is always a proper solvent‐antisolvent couple for the studied solute) ensures future developments for very different types of materials. PGSS uses the fact that it is much easier to dissolve CO2 in organic solutions (or melted compounds) than the contrary. It presents very promising perspectives of industrial development. After almost 20 years of active research, and more than 10 years of process development, this technology is reaching maturity, and very soon commercial drug produced by these techniques are likely to appear.
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Jacques Fages, Hubert Lochard, Jean‐jacques Letourneau, Martial Sauceau, Élisabeth Rodier. Particle generation for pharmaceutical applications using supercritical fluid technology. Powder Technology, Elsevier, 2004, 141 (3), pp.219-226. ⟨10.1016/j.powtec.2004.02.007⟩. ⟨hal-01668423⟩



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