Current Treatments for COVID-19: Application of Supercritical Fluids in the Manufacturing of Oral and Pulmonary Formulations

Abstract

Even though more than two years have passed since the emergence of COVID-19, the research for novel or repositioned medicines from a natural source or chemically synthesized is still an unmet clinical need. In this review, the application of supercritical fluids to the development of novel or repurposed medicines for COVID-19 and their secondary bacterial complications will be discussed. We envision three main applications of the supercritical fluids in this field: (i) drug micronization, (ii) supercritical fluid extraction of bioactives and (iii) sterilization. The supercritical fluids micronization techniques can help to improve the aqueous solubility and oral bioavailability of drugs, and consequently, the need for lower doses to elicit the same pharmacological effects can result in the reduction in the dose administered and adverse effects. In addition, micronization between 1 and 5 µm can aid in the manufacturing of pulmonary formulations to target the drug directly to the lung. Supercritical fluids also have enormous potential in the extraction of natural bioactive compounds, which have shown remarkable efficacy against COVID-19. Finally, the successful application of supercritical fluids in the inactivation of viruses opens up an opportunity for their application in drug sterilization and in the healthcare field.

Keywords: COVID-19; bioactive components; micronization; sterilization; supercritical fluids.

Figure 3

The rapid expansion of supercritical solvent (RESS) process (adapted from Parhi and Suresh [145]).

Figure 1

Schematic representation of the SARS-CoV-2 virus life cycle (adapted from Abu-Farha, 2020 [21]).

Figure 2

Drugs and their target within the different stages of the SARS-CoV-2 viral cycle.

Figure 4

Particles from gas-saturated solutions (PGSS) process (adapted from Martin and Cocero [123]).

Figure 5

Concentrate Powder Form (CPF) process (adapted from Vorobei and Parenago [141]).

Figure 6

Continuous Powder Coating Spraying Process (CPCSP) (adapted from Nunes and Duarte [139]).

Figure 7

Depressurization of an Expanded Liquid Organic Solution (DELOS) process (adapted from Costa et al. [137]).

Figure 8

CO₂-Assisted Nebulization with a Bubble Dryer (CAN-BD) process (adapted from Costa et al. [137]).

Figure 9

Supercritical-Enhanced Atomization (SEA) process (adapted from Padrela et al. [15]).

Figure 10

Supercritical Fluid-Assisted Atomization (SAA) process (adapted from Franco et al. [135]).

Figure 11

Gaseous antisolvent (GAS) process.

Figure 12

Supercritical Antisolvent (SAS) process (adapted from Martin and Cocero [123]).

Figure 13

Solution-Enhanced Dispersion by Supercritical Fluids (SEDS) process (adapted from Tran and Park [181]).

Figure 14

Supercritical Fluid Extraction of Emulsions (SFEE) process (adapted from Prieto et al. [185]).