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

Abstract

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 to 338 K) and pressures (120 to 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 × 10−6 to 14.25 × 10−6, resulting in solubilities between 0.015 - 0.120 g/L. Correlations between the experimental results were made using three different models: (1) six models of density-based (Chrastil, Méndez–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 (〖∆H〗_"vap" ), total (〖∆H〗_"tot" ), and solvation (〖∆H〗_"sol" ) enthalpies were computed.