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

Abstract

Solid 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 practical values. Furthermore, the FEL–SOL solid dispersions were subjected to accelerated stability studies for up to 3 months.

• Felodipine
• Flory–Huggins theory
• ketoconazole
• miscibility/solubility
• phase diagram
• physical stability
• solid dispersions
• Soluplus®

Acknowledgements

The authors would like to thank Dr. Yanbin Huang from the Department of Chemical Engineering, Tsinghua University and Long Chen from the Department of Chemical Engineering, Princeton University for their valuable assistance concerning the calculations for the phase diagrams. The authors would also like to thank BASF for its generous supply of Soluplus® and technical assistance.

Declaration of interest

The authors report no declarations of interest.