An overview on the application of supercritical carbon dioxide for the processing of pharmaceuticals

Abstract

Supercritical carbon dioxide (scCO2) application in the pharmaceutical industry is still undeveloped regardless of significant research interests in this processing medium shown in the last decades. ScCO2 technologies can improve drug solubility, bioavailability, and therapeutic effect. These technologies can lead to the development of new formulations that will contribute to a decrease in drug dose, medication frequency, and increase patients' well-being. Considering the significant decrease in the price of high-pressure equipment and society's growing need for cleaner production and safer products, it is expected that symbiosis between supercritical fluid and pharmaceutical technologies will happen soon. Therefore, this review was focused on the latest contributions of scCO2 technologies to the pharmaceutical field. The main aim was to bring these technologies closer to pharmaceutical specialists. For this purpose, the most commonly used technologies were explained and discussed: the preparation of solid dispersions, polymer impregnation with drugs, and drug micro/nanoparticle production using scCO2.

Green Processing of Neat Poly(lactic acid) Using Carbon Dioxide under Elevated Pressure for Preparation of Advanced Materials: A Review (2012–2022)

“…The preparation of PLA particles using CO 2 under elevated pressure avoids issues associated with conventional methods for particle generations such as long processing time, unwanted particle morphologies, particle agglomeration, undesired amorphous or crystalline forms, etc. [ 86 , 87 ]. Techniques for the generation of PLA particles use d-CO 2 and sc-CO 2 , both as a solvent and anti-solvent.…”

“…The PGSS process allows the formation of particles in several steps: (1) the polymer is melted or dissolved in an extruder or a vessel and transferred using a dosing system to a static mixer, (2) the CO 2 under elevated pressure is pumped into the same static mixer where both flows are homogenized, and (3) the CO 2 -saturated mixture/solution is depressurized through a nozzle into a spray tower [ 86 , 91 , 92 , 93 ]. The nozzle construction enables the formation of fine droplets that become solidified due to the cooling effect of the expanding gas, i.e., polymer particles are precipitated based on the Joule–Thomson effect.…”

“…The organic solvent is then eliminated from the system along with CO 2 . The choice of the organic solvent for the SAS process is crucial [ 86 ], as it may have good miscibility with sc-CO 2 and PLA at the selected process conditions. PLA micron and submicron particles generated by using SAS are mainly solvent-free.…”

“…If the solubility of a BC in sc-CO 2 is low for the PLA impregnation process, it could be improved by the addition of a polar co-solvent such as ethanol [ 124 , 125 ]. After contact between a polymeric material and a BC for a certain soaking time, sc-CO 2 can be completely removed from the obtained material by a pressure decrease, while BC will remain within the polymer matrix due to precipitation or chemical bonding [ 86 , 126 ]. The supercritical solvent impregnation process (SSI) has significant advantages compared to conventional impregnation processes associated with sc-CO 2 properties.…”