L S Taylor1, G Zografi. 1. School of Pharmacy, University of Madison-Wisconsin 53706, USA.
Abstract
PURPOSE: To study the molecular structure of indomethacin-PVP amorphous solid dispersions and identify any specific interactions between the components using vibrational spectroscopy. METHODS: Solid dispersions of PVP and indomethacin were prepared using a solvent evaporation technique and IR and FT-Raman spectra were obtained. RESULTS: A comparison of the carbonyl stretching region of gamma indomethacin, known to form carboxylic acid dimers, with that of amorphous indomethacin indicated that the amorphous phase exists predominantly as dimers. The hydrogen bonding of alpha indomethacin is not as dimers. Addition of PVP to amorphous indomethacin increased the intensity of the infrared band assigned to non-hydrogen bonded carbonyl. Concomitantly, the PVP carbonyl stretch appeared at a lower wavenumber indicating hydrogen bonding. Model solvent systems aided spectral interpretation. The magnitude of the spectral changes were comparable for an indomethacin-PVP solid dispersion and a solution of indomethacin in methylpyrrolidone at the same weight percent. CONCLUSIONS: Indomethacin interacts with PVP in solid dispersions through hydrogen bonds formed between the drug hydroxyl and polymer carbonyl resulting in disruption of indomethacin dimers. PVP may influence the crystallisation kinetics by preventing the self association of indomethacin molecules. The similarity of results for solid dispersions and solutions emphasises the "solution" nature of this binary amorphous state.
PURPOSE: To study the molecular structure of indomethacin-PVP amorphous solid dispersions and identify any specific interactions between the components using vibrational spectroscopy. METHODS: Solid dispersions of PVP and indomethacin were prepared using a solvent evaporation technique and IR and FT-Raman spectra were obtained. RESULTS: A comparison of the carbonyl stretching region of gamma indomethacin, known to form carboxylic acid dimers, with that of amorphous indomethacin indicated that the amorphous phase exists predominantly as dimers. The hydrogen bonding of alpha indomethacin is not as dimers. Addition of PVP to amorphous indomethacin increased the intensity of the infrared band assigned to non-hydrogen bonded carbonyl. Concomitantly, the PVP carbonyl stretch appeared at a lower wavenumber indicating hydrogen bonding. Model solvent systems aided spectral interpretation. The magnitude of the spectral changes were comparable for an indomethacin-PVP solid dispersion and a solution of indomethacin in methylpyrrolidone at the same weight percent. CONCLUSIONS:Indomethacin interacts with PVP in solid dispersions through hydrogen bonds formed between the drug hydroxyl and polymer carbonyl resulting in disruption of indomethacin dimers. PVP may influence the crystallisation kinetics by preventing the self association of indomethacin molecules. The similarity of results for solid dispersions and solutions emphasises the "solution" nature of this binary amorphous state.