The study investigates the molecular interactions between polyvinylpyrrolidone (PVP) and indomethacin in amorphous solid dispersions using vibrational spectroscopy. Solid dispersions were prepared via solvent evaporation and analyzed with infrared (IR) and FT-Raman spectroscopy. The results show that amorphous indomethacin predominantly exists as dimers, while α-indomethacin does not. Adding PVP to amorphous indomethacin increases the intensity of the infrared band for non-hydrogen bonded carbonyl groups and shifts the PVP carbonyl stretch to a lower wavenumber, indicating hydrogen bonding. Model solvent systems helped interpret the spectra, and the spectral changes in solid dispersions were comparable to those in solutions of indomethacin in methylpyrrolidone at the same concentration. The study concludes that PVP interacts with indomethacin through hydrogen bonds between the drug's hydroxyl and polymer's carbonyl groups, disrupting indomethacin dimers. PVP may also influence crystallization by preventing self-association of indomethacin molecules. The similarity between solid dispersions and solutions highlights the "solution-like" nature of the binary amorphous state. Indomethacin exists as two polymorphs, γ and α, and in amorphous form. The γ form forms cyclic dimers via hydrogen bonding, while the α form does not. Vibrational spectroscopy is a reliable method for characterizing polymorphs and crystallinity. The study shows differences in the vibrational spectra of the three forms, with the amorphous form showing a pattern closer to the α form than the γ form. The OH stretching region in the infrared spectrum shows a broad band between 3400 and 2500 cm⁻¹, characteristic of hydrogen-bonded hydroxyl groups. The C=O stretch region (1750–1600 cm⁻¹) shows differences between the polymorphs, with the γ form having a higher frequency for the benzoyl group due to mesomerism. The study emphasizes the importance of using amorphous form spectra as a reference for understanding interactions in amorphous binary systems.The study investigates the molecular interactions between polyvinylpyrrolidone (PVP) and indomethacin in amorphous solid dispersions using vibrational spectroscopy. Solid dispersions were prepared via solvent evaporation and analyzed with infrared (IR) and FT-Raman spectroscopy. The results show that amorphous indomethacin predominantly exists as dimers, while α-indomethacin does not. Adding PVP to amorphous indomethacin increases the intensity of the infrared band for non-hydrogen bonded carbonyl groups and shifts the PVP carbonyl stretch to a lower wavenumber, indicating hydrogen bonding. Model solvent systems helped interpret the spectra, and the spectral changes in solid dispersions were comparable to those in solutions of indomethacin in methylpyrrolidone at the same concentration. The study concludes that PVP interacts with indomethacin through hydrogen bonds between the drug's hydroxyl and polymer's carbonyl groups, disrupting indomethacin dimers. PVP may also influence crystallization by preventing self-association of indomethacin molecules. The similarity between solid dispersions and solutions highlights the "solution-like" nature of the binary amorphous state. Indomethacin exists as two polymorphs, γ and α, and in amorphous form. The γ form forms cyclic dimers via hydrogen bonding, while the α form does not. Vibrational spectroscopy is a reliable method for characterizing polymorphs and crystallinity. The study shows differences in the vibrational spectra of the three forms, with the amorphous form showing a pattern closer to the α form than the γ form. The OH stretching region in the infrared spectrum shows a broad band between 3400 and 2500 cm⁻¹, characteristic of hydrogen-bonded hydroxyl groups. The C=O stretch region (1750–1600 cm⁻¹) shows differences between the polymorphs, with the γ form having a higher frequency for the benzoyl group due to mesomerism. The study emphasizes the importance of using amorphous form spectra as a reference for understanding interactions in amorphous binary systems.