Differences in the interaction between aryl propionic acid derivatives and poly(vinylpyrrolidone) K30: A multi-methodological approach

The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and (13)C-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, NAP, and the least for FEN. The interaction of comelted. drug and PVP was studied by differential scanning calorimetry by applying the Gordon-Taylor equation, which revealed that small molar drug volumes may favour the drug diffusion through the PVP amorphous chains increasing the polymer free volume and decreasing the mixture T, The molecular docking study revealed that intermolecular energy is mainly due to the contribution of van der Waals energy component, causing the differences among the drugs, and is related to the drug-PVP surface contact area in the complex formed. Solid-state kinetic study demonstrated that IBP molecules are involved in a three-dimensional diffusion mechanism within the polymer favoured by its low molar volume that reduces molecular hindrance, and by the weakness of its crystal lattice, which facilitates crystallinity loss and stabilisation of the amorphous phase.