Amorphous Solid Dispersion Using Supercritical Fluid Technology

Abstract

Use of supercritical fluid (SCF) processing technologies in the pharmaceutical industry has seen remarkable growth as an alternate technology for the preparation of micro- and nano-sized particles. Carbon dioxide, having low critical temperature (31.2 °C) and pressure (73.8 bar or 7.4 Mpa) and being nonflammable, nontoxic, and environmentally safe, is the choice of SCF for processing of pharmaceuticals including heat-sensitive materials such as biologicals. Depending on how SCF is used in the technology, a number of variations have emerged to meet the needs of the compound and the product design. For example, SCF can act either as a solvent, an antisolvent, or as a solute. The superior solvent characteristics of SCF stem from its physical properties where it behaves like a gas and liquid at the same time. The high diffusivity and low viscosity coupled with low surface tension helps in solubilizing the organic compounds. SCF technologies can be grouped into several categories based on the particle growth mechanism and their collection environment. Rapid expansion of supercritical solutions, gas antisolvent (GAS) precipitation, supercritical antisolvent (SAS) precipitation, precipitation with compressed fluid antisolvent (PCA), solution-enhanced dispersion by SCF (SEDS), and precipitation from gas-saturated solutions (PGSS) are the main variants of SCF technologies. These techniques have successfully produced micro- and nanoparticles as well as amorphous solid dispersions (ASDs). In addition to being a stand-alone processing technology, SCF has been frequently used as a processing aid in the manufacture of the ASD, for instance, as temporary plasticizer in the melt extrusion process to reduce the processing temperature, melt viscosity, or to impart porosity. The premise of this chapter is to examine the potential of SCF in producing amorphous dispersions and to identify the opportunities for future development.