ABSTRACT

Particle generation may be performed by expansion, for example, RESS or PGSS, or by dilution of liquids by dense gases, for example, GAS or SAS. Precipitation techniques in scCO2 have already been investigated quite in detail for pure model and real substances, but interdependences between several compounds in composite products are less known. This chapter illustrates the basis of the most important scCO2 precipitation techniques for the generation of powders and composites, particularly those with applications in the pharmaceutical industry. The bioavailability of pharmaceuticals presented in a solid formulation strongly depends on the size, particle size distribution, and morphology of the particles and, thus, on the used precipitation technique.

Several supercritical fluid (SCF) nonreactive spray precipitation processes are now under development, involving many pharmaceutical applications. The SCF is used as a precipitation medium for materials recrystallization or composite product formation. Spray processes, supported by compressed CO2, allow for the generation of powders and composites with characteristics different from those obtained using conventional methods. Next, the different concepts used for SCF particle design are shortly described in order to clarify a rather confusing domain where many similar processes are designated by different acronyms. Process design is strongly dependent on the solubility of CO2 of the ingredients to be precipitated [1-6]. 4.1.1 Supercritical Fluid as a SolventProcesses designed for compounds soluble in supercritical carbon dioxide (scCO2) consist of dissolving the product in a compressed fluid at pressures in the order of 150-300 MPa and rapidly depressurizing the formed solution. This process takes advantage of the large variations in the solvent power of the SCF with changes in pressure. 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 scCO2 (low-molecular-weight and low-polarity organic or organometallic compounds). Even in the most favorable cases, the production capacity of these processes is limited. This problem can be alleviated by the use of a cosolvent, but in this case the benefit of the total elimination of the organic solvent is lost. RESS: This acronym refers to rapid expansion of supercritical solutions. The depressurization is carried out through an adequate nozzle, causing an extremely rapid nucleation of the product into a highly dispersed material. 4.1.2 Supercritical Fluid as an AntisolventProcesses designed for compounds with negligible solubility in scCO2. The SCF is not used as a solvent but as an antisolvent that