Accelerated Stability of an X-Ray Amorphous Frusemide-Polyvinylpyrrolidone Solid Dispersion

An accelerated stability study compared the chemical, solid state and physicochemical stability of an X-ray amorphous frusemide-polyvinylpyrrolidone (PVP) solid dispersion system (the test system) with a standard frusemide sample during storage for 12 months at 6, 20, 30, 37 and 45°CNo chemical degradation was found in any sample and the drug phase in the solid dispersion was shown by X-ray analysis to remain in the amorphous or non-crystalline state even after storage for 12 months at up to 45°C and 40%RH. DSC data for the test dispersion demonstrated a change in the PVP-moisture endotherm after storage for 12 months at 37° and 45°C, while a lack of frusemide endotherms confirmed X-ray data which indicated the presence of an amorphous drug phase. IR analyses indicated that the intermolecular frusemide-PVP hydrogen bond interaction in the solid state remained intact during the study leading to the conclusion that the specific drug-polymer interaction retards or inhibits drug recrystallisation by reducing molecular motion in the solid state. The dissolution rate of the test dispersion was found not to decrease during the study reflecting the stability of the X-ray amorphous drug phaseWhilst the combination of high humidity (75%RH) and high temperature (45°C) was found to be detrimental to the physical state of the amorphous frusemide-PVP dispersion, provided moisture-resistent packaging is used for these pharmaceutical formulations, acceptable shelf lives are predicted