Improving and measuring the solubility of favipiravir and montelukast in SC-CO(2) with ethanol projecting their nanonization

Supercritical carbon dioxide (SC-CO(2))-based approaches have become more popular in recent years as alternative methods for creating micro- or nanosized medicines. Particularly, high drug solubility is required in those techniques using SC-CO(2) as a solvent. During the most recent pandemic years, favipiravir and montelukast were two of the most often prescribed medications for the treatment of COVID-19. In this study, ethanol at 1 and 3 mol% was utilized as a cosolvent to increase the solubility of both medicines in SC-CO(2) by a static approach using a range of temperatures (308 to 338 K) and pressure (12 to 30 MPa) values. The experimentally determined solubilities of favipiravir and montelukast in SC-CO(2) + 3 mol% ethanol showed solubility values up to 33.3 and 24.5 times higher than that obtained for these drugs with only SC-CO(2). The highest values were achieved in the pressure of 12 MPa and temperature of 338 K. Last but not least, six density-based semi-empirical models with various adjustable parameters were used to perform the modeling of the solubility of favipiravir and montelukast.