Application of the Vrentas-Duda free-volume theory of diffusion below the glass-transition temperature: Application to hypromellose acetate succinate-solvent systems

The Vrentas-Duda free-volume theory for diffusion characterizes the diffusivity of a solvent in a polymer in terms of the concentration and size of the solvent, the temperature, and the glass transition temperature (T-g) of the individual components. The effective T-g of the polymer, however, is a function of the concentration of the solvent. This article introduces a modification that corrects for this change in the glass-transition temperature, thus providing more accurate diffusivities. The model has been verified by comparison with experimental diffusivities of water, acetone, methanol, and tetrahydrofuran in hypromellose acetate succinate (HPMCAS). HPMCAS is widely used in the production of pharmaceutical formulations. One common application is the formation of amorphous solid dispersions with poorly soluble active pharmaceutical ingredients (APIs) for dissolution and solubility enhancement. Frequently, the APIs and HPMCAS are put into solution and spray dried at an outlet temperature below the normal glass-transition temperature. The modified free-volume theory is able to directly predict or correlate with only one adjustable parameter the diffusivities as a function of the concentration and temperature. (c) 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47351.