Investigation of phase diagrams and physical stability of drug–polymer solid dispersions

AbstractSolid dispersion technology has been widely explored to improve the solubility and bioavailability of poorly water-soluble compounds. One of the critical drawbacks associated with this technology is the lack of physical stability, i.e. the solid dispersion would undergo recrystallization or phase separation thus limiting a product’s shelf life. In the current study, the melting point depression method was utilized to construct a complete phase diagram for felodipine (FEL)–Soluplus® (SOL) and ketoconazole (KTZ)–Soluplus® (SOL) binary systems, respectively, based on the Flory–Huggins theory. The miscibility or solubility of the two compounds in SOL was also determined. The Flory–Huggins interaction parameter χ values of both systems were calculated as positive at room temperature (25 °C), indicating either compound was miscible with SOL. In addition, the glass transition temperatures of both solid dispersion systems were theoretically predicted using three empirical equations and compared with the p...