Water diffusion through the matrix of three superdisintegrants, namely sodium starch glycolate (SSG), croscarmellose sodium (cCMC-Na) and crospovidone (cPVP), was studied at the sub-molecular level using Attenuated Total Reflectance (ATR)-FTIR spectroscopy and molecular dynamics simulations, and the results were correlated to water uptake studies conducted at the particulate level using Parallel Exponential Kinetics (PEK) modeling in dynamic moisture sorption studies and optical microscopy. ATR-FTIR studies indicated that water diffuses inside cPVP by a single fast acting process, while in SSG and cCMC-Na, a slow and a fast process acting simultaneously, were identified. The same pattern regarding the rate of water uptake for all superdisintegrants was found also at the particulate level by PEK modeling. Moreover, molecular dynamics simulation helped elucidate the hydrogen bonding patterns formed between water-SSG and water-cCMC-Na, mainly via their carboxylic oxygen atoms and secondarily via their hydroxyl groups, while cPVP formed hydrogen bonds only through carbonyl oxygen. Finally, cPVP chains showed significant flexibility during hydration, while cCMC-Na and SSG chains retain their conformation to some extent, explaining the extensive swelling observed also at the particulate level by optical microscopy hydration studies.
Keywords: ATR–FTIR spectroscopy; Superdisintegrants; diffusion; moisture sorption; molecular dynamics.