Enhancement of the Physical and Chemical Stability of Amorphous Drug–Polymer Mixtures via Cryogenic Comilling

Abstract

Amorphous dispersions of the Biclotymol antiseptic are obtained in polyvinylpyrrolidone (PVP), for different drug loadings, by comilling at temperatures below the glass transition of both components. Characterization of the dispersions by scanning differential calorimetry and temperature-dependent broadband dielectric spectroscopy shows them to be homogeneous amorphous molecular mixtures. A single glass transition with pronounced enthalpy recovery peak is observed, indicative of the formation of a homogeneous glass state characterized by substantial aging. The polymer has a considerable antiplasticizing effect on the drug, increasing its glass transition temperature (Tg) to well above room temperature. The Tg of the mixture increases linearly with the macromolecular mass fraction. Three (macro)molecular relaxations are identified in the isothermal dielectric spectra of the mixtures. The slowest process corresponds to the cooperative (α relaxation) dynamics of the polymer chains and drug molecules simultan...