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PURPOSE In a recent paper, we have explored that indomethacin (IMC) effectively acted as a crystallization inhibitor for polyethylene glycol 6000 (PEG)1 despite the fact that the absence of interaction between the drug and the carrier in the solid state was reported in the literature. We hypothesize that the interaction between the two components must exist. METHODS Dispersions made up of IMC and PEG were prepared by heating the mixture of the drug and the carrier to above the melting temperatures of both components, followed by solidification of the melt. Drug-carrier interaction was characterized by variable temperature Fourier transform infrared spectroscopy (FTIR) and solid state 13C nuclear magnetic resonance (NMR) spectroscopy. RESULTS FTIR data show the strong interaction between IMC and PEG in molten state. This interaction is disrupted upon storage (and solidification), resulting in segregation of IMC from PEG crystals. This is further confirmed by NMR. Surprisingly, each ether oxygen of the PEG unit can form hydrogen bonds with two IMC molecules, owing to the perfect arrangement of drug molecules along the carrier chains that in turn is originating from π-π stacking between aromatic rings of neighbouring IMC molecules. When the hydroxyl group of IMC is substituted by a methoxy group, no interaction between the new compound and PEG can be detected and the methoxy derivative of IMC is unable to inhibit crystallization of PEG. CONCLUSION This work demonstrates the presence of hydrogen bonding between IMC and PEG in molten state, and the disruption of the bonds upon crystallization of the carrier. Furthermore, both the presence of a hydrogen bonding forming center and an aromatic ring of IMC are required for the crystallization inhibition effect on PEG. REFERENCES 1. Duong TV, Van Humbeeck J, Van den Mooter G. Crystallization kinetics of indomethacin/polyethylene glycol dispersions containing high drug loadings, Mol. Pharm. 12(7), 2493-504 (2015).