Recent Patents on Engineering 2008, 2, 9-20 9 1872-2121/08 $100.00+.00 © 2008 Bentham Science Publishers Ltd. Precipitation Processes with Supercritical Fluids: Patents Review Angel Martín and Maria J. Cocero* Departamento de Ingeniería Química y Tecnología del Medio Ambiente, Facultad de Ciencias, Universidad de Valladolid, 47011 Valladolid, Spain Received: December 3, 2007; Accepted: December 10, 2007; Revised: December 13, 2007 Abstract: Supercritical fluid techniques for materials precipitation have been proposed as an alternative to conventional precipitation processes as they can improve the performance of these processes in terms of reduction of particle size and control of morphology and particle size distribution, without degradation or contamination of the product. These techniques have received much attention during the last years, and their feasibility and performance have been proved for many substances. Several precipitation technologies, in which the supercritical fluid plays different roles (solvent, anti solvent, co solvent, solute, atomization agent…) have been developed. This article presents a review of the patents related to supercritical precipitation technologies, with emphasis on the description of the different precipitation methods and mechanisms exploited by these technologies, and on the technical solutions given for the practical problems of the technologies. Keywords: Micronization, particle design, supercritical carbon dioxide, RESS, GAS, SAS, PGSS. INTRODUCTION The ability to produce micro or nano particles with a controlled morphology and particle size distribution is essential for many applications, as for example the pro- duction of advanced ceramic or polymeric materials with improved mechanical or structural properties, the manu- facture of catalyst particles with high specific surface area, the micronization of dyes or explosives, the production of innovative food additives etc. A particularly important appli- cation is the micronization of pharmaceuticals. The bio- availability and dosage of these substances can be improved by producing a formulation with small and controlled particle size, and the development of better micronization technologies can also allow designing new pharmaceutical formulations or using alternative administration routes. Supercritical fluids (SCF) are a very convenient medium for many of these applications. This is a consequence of the properties of supercritical fluids in general and supercritical carbon dioxide (SC-CO 2 ), the most used supercritical fluid, in particular [1]: SC-CO 2 is non-toxic and can be easily and completely removed from the solid product as a gas simply by depressurization, a very convenient property for applications concerning products for human consumption as pharmaceuticals or food additives, in which to avoid the contamination of the product by toxic solvents is an important issue. SC-CO 2 provides an inert medium suitable for processing materials that are susceptible to oxidation, and also for difficult-to-comminute materials as explosives. Furthermore, the low critical temperature of CO 2 (304.2 K) allows to carry out processes with SC-CO 2 at near ambient temperatures, thus avoiding degradation of heat-sensitive materials. In addition to these properties, it is possible to vary the physical properties of SC-CO 2 , and in particular its *Address correspondence to this author at the Departamento de Ingeniería Química y Tecnología del Medio Ambiente, Facultad de Ciencias, Universidad de Valladolid, 47011 Valladolid, Spain; Tel: (+34) 983-423- 174; Fax: (+34) 983-423-013; E-mail: mjcocero@iq.uva.es solvent power, with changes in pressure and temperature. This possibility can be advantageously used to develop several precipitation technologies that make possible to produce a very high and homogeneous supersaturation, thus leading to the precipitation of particles with a small and regular size [2]. Although SC-CO 2 is the most frequently used supercritical fluid for precipitation processes, other supercritical fluids such as ethane, ethylene, dimethyl ether, propane, nitrous oxide, hexafluoroethane, etc. are also suit- able for this purpose and may be advantageous in certain applications, and most patents of supercritical fluid precipi- tation processes claim the operation with a wide variety of supercritical fluids. Since the development of the first supercritical precipi- tation technologies in the late 80s, this field has grown to become one of the most studied applications of supercritical fluids, as a natural consequence of the commercial interest of these applications. This article presents a review of patents related to supercritical precipitation technologies that reflect the evolution of these technologies and their current status. The different supercritical precipitation processes that will be presented are classified according to the role of the super- critical fluid in the process: solvent, anti-solvent, solute, or co-solvent [3]. The discussion and presentation of the patents is organized around the aspect of the process that they discuss, the features that they try to improve or the technical prob- lems that they try to solve, rather than in a strict chronolo- gical order. Since the patents filed before year 2000 were already reviewed by Jung and Perrut [4], this review is focused in the patents filed after this date, although some of the most representative patents previous to year 2000 are also mentioned when it is necessary for the completeness and coherence of the discussion. The review does not pretend to be exhaustive, and in general only the patents that introduce new technologies or methods are discussed. The patents that describe the application of previously available technologies for the processing of a specific material are omitted, unless