Solubility of pazopanib hydrochloride (PZH, anticancer drug) in supercritical CO2: Experimental and thermodynamic modeling

It is essential to understand drug compounds' solubility and other properties to formulate and create a supercritical fluid-based technology that can produce micro or nanosized particles of the pharmaceutical substance. Accordingly, at temperatures (308-338 K) and pressures (120-270 bar), the solubility of anticancer drug, pazopanib hydrochloride (PZH), in supercritical carbon dioxide (Sc-CO2) was experimentally investigated, for the first time. PZH dissolved (in the Sc-CO2 mole fractions) ranged from 1.87 x 10(-6) to 14.25 x 10(-6), resulting in solubilities between 0.015 and 0.120 g/L. Correlations between the experimental results were made using three different models: (1) six models of density-based (Chrastil, Mendez-Santiago & Teja (MST), Bartle et al., Kumar-Johnston, Alwi-Garlapati, and Sodeifian et al.), (2) solid-liquid equilibrium models (expanded liquid model proposed by Sodeifian et al., and Flory-Huggins theory with modified solubility parameters), and (3) equation of state (EoS) (PR with vdW2 mixing rule). All examined models were able to produce acceptable fits with the data at a satisfactory level of precision; however, the empirical density-based model proposed by Sodeifian et al., was found superior in terms of the AARD% criterion. In addition, the vaporization (Delta H-vap), total (Delta H-to(t)) and solvation (Delta H-sol) enthalpies were computed.