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Updated: Oct 3, 2025

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Measuring and Modeling Water Sorption in Amorphous Indomethacin and Ritonavir
Dominik Borrmann1, Andreas Danzer1, Gabriele Sadowski1
1Department of Chemical and Biochemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Str. 70, Dortmund D-44227, Germany.
Abstract:
The amorphous state of an active pharmaceutical ingredient (API) enhances its water solubility compared to its crystalline state. However, it is well known that amorphous substances can absorb significant amounts of water therewith inducing API recrystallization. This work explores methods to obtain reliable information about water sorption in amorphous APIs and its modeling. Experimental water-sorption curves over a broad humidity range were obtained by measuring the mass increase of well-defined films of amorphous APIs. Water-sorption isotherms modeled using perturbed-chain statistical associating fluid theory (PC-SAFT) showed better accordance with the experimental data than those obtained using the Flory-Huggins model. Crank's diffusion equation was used to describe the water-sorption kinetics providing Fickian diffusion coefficients of water in indomethacin and in ritonavir. Stefan-Maxwell diffusion coefficients were obtained by converting Fickian diffusion coefficients using water activity coefficients obtained from PC-SAFT. Finally, the free-volume theory was applied to explain the persistent water concentration dependency of the Stefan-Maxwell diffusion coefficients.
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