Phase behavior, intermolecular interaction, and solid state characterization of amorphous solid dispersion of Febuxostat

Abstract

The aim of this work was to prepare and characterize the amorphous molecular dispersion of Febuxostat (FXT) using PVP K30, HPMC-AS, Soluplus®, and PVP VA64. The solid dispersions were prepared by solvent evaporation technique. Their physical properties were studied by differential scanning calorimetry, powder X-ray diffraction, Fourier transformation infrared spectroscopy, and compared to that of same physical mixtures. The success of physicochemical stability of the dispersions is often revealed as glass transition temperature (T_g) versus composition (w) dependencies. The shape of the T_g versus composition was mathematically modeled using the Gordon-Taylor equation, Couchman-Karasz equation, Brekner-Schneider-Cantow equation, and a three-parameter BCKV equation. In this work, different types of T_g patterns obtained for FXT-polymer binary mixtures are analyzed in terms of the above equations and relations between their prime fitting parameters are presented. The theoretical values and modeled parameters were compared using various results obtained by thermal analysis. The influence of important physicochemical phenomena and properties of the mixtures on the shape of the T_g versus composition patterns are also illustrated. The interaction between drug and polymers and the model parameters were analyzed, aiming to assess the state of mixing and intermolecular interactions.

Keywords: Amorphous solid dispersions; drug–polymer interactions; glass transition; hydrogen bonding; infrared spectroscopy; miscibility.