Water Vapor Absorption into Amorphous Hydrophobic Drug/Poly(vinylpyrrolidone) Dispersions

Abstract

Water vapor absorption isotherms were measured for three amorphous hydrophobic drug/poly(vinylpyrrolidone) (PVP) dispersions in the concentration range 10–90% w/w PVP. Experimental isotherms were compared to predicted isotherms calculated using each individual component isotherm multiplied by its weight fraction. Indomethacin (IMC)/PVP, ursodeoxycholic acid (UDCA)/PVP and indapamide (IDP)/PVP amorphous dispersions all exhibited experimental isotherms reduced relative to predicted isotherms indicating that dispersion formation altered the water vapor absorption properties of the individual components. For all three drug/PVP systems, deviation from predicted water uptake was greatest close to the 1:1 drug:PVP monomer composition, indicating that intermolecular interaction in amorphous dispersions affects the water uptake properties of the individual components. Using dry glass transition temperature (Tg) data, the extent of drug/PVP interaction was shown to be greatest in the IDP/PVP system, which could explain why the largest reduction in water vapor absorption was found in this system. The plasticizing effect of absorbed water varied according to dry dispersion PVP content in all systems and the resulting nonideal changes in free volume, calculated using the Vrentas model, were greatest close to the 1:1 drug:PVP monomer composition. A three‐component Flory–Huggins model successfully predicted isotherms for IMC/PVP compositions from 60 to 90% w/w PVP and identified an IMC–PVP interaction parameter χ in the range 1.27–1.49, values that suggest poor homogeneity of mixing in the dry system. These data indicate that amorphous dispersion formation causes both chemical and physical changes in the individual amorphous components that can have a significant effect on their water vapor absorption properties. © 2002 Wiley‐Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2150–2165, 2002