Particle design using supercritical fluids: Literature and patent survey

As particle design is presently a major development of supercritical fluids applications, mainly in the pharmaceutical, nutraceutical, cosmetic and specialty chemistry industries, number of publications are issued and numerous patents filed every year. This document presents a sun;ey (that cannot pretend to be exhaustive!) of published knowledge classified according to the different concepts currently used to manufacture particles, microspheres or microcapsules. liposomes or other dispersed materials (like microfibers): RESS: This acronym refers to 'Rapid Expansion of Supercritical Solutions'; this process consists in solvating the product in the fluid and rapidly depressurizing this solution through an adequate nozzle, causing an extremely rapid nucleation of the product into a highly dispersed material. Known for long, this process is attractive due to the absence of organic solvent use; unfortunately, its application is restricted to products that present a reasonable solubility in supercritical carbon dioxide (low polarity compounds). GAS or SAS: These acronyms refer to 'Gas (or Supercritical fluid) Anti-Solvent; one specific implementation being SEDS ('Solution Enhanced Dispersion by Supercritical Fluids'); this general concept consists in 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. According to the solid morphology that is wished, various ways of implementation are available: GAS or SAS recrystallization: This process is mostly used for recrystallization of solid dissolved in a solvent with the aim of obtaining either small size particles or large crystals, depending on the growth rate controlled by the anti-solvent pressure variation rate: ASES: This name is rather used when micro- or nano-particles are expected; the process consists in pulverizing a solution of the substrate(s) in an organic solvent into a vessel swept by a supercritical fluid; SEDS: A specific implementation of ASES consists in co-pulverizing the substrate(s) solution and a stream of supercritical carbon dioxide through appropriate nozzles. PGSS: This acronym refers to 'Particles from Gas-Saturated Solutions (or Suspensions)': This process consists in dissolving a supercritical fluid into a liquid substrate, or a solution of the substrate(s) in a solvent, or a suspension of the substrate(s) in a solvent followed by a rapid depressurization of this mixture through a nozzle causing the formation of solid particles or liquid droplets according to the system. The use of supercritical fluids as chemical reaction media for material synthesis. Two processes are described: thermal decomposition in supercritical fluids and hydrothermal synthesis. We will successively detail the literature and patents for these four main process concepts, and related applications that have been claimed. Moreover, as we believe it is important to take into account the user's point-of-view, we will also present this survey in classifying the documents according three product objectives: particles (micro- or nano-) of a single component, microspheres and microcapsules of mixtures of active and carrier (or excipient) components, and particle coating. (C) 2001 Eisevier Science B.V. All rights reserved.