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UNDERSTANDING SOLID STATE INTERACTIONS OF CO-AMORPHOUS INDOMETHACIN AND NAPROXEN WITH THE USE OF QUANTUM MECHANICAL CALCUATIONS AND INFRARED SPECTROSCOPY
Published: 18 April 2012 by MDPI in The 2nd Electronic Conference on Pharmaceutical Sciences session Advances in the solid state field
Abstract: Co-amorphous drug systems have recently shown to be a potential new strategy in stabilizing the amorphous state of a drug and increasing its apparent dissolution. The improved properties of these systems, when compared to the single amorphous drug, were attributed to molecular interactions between the drug and its co-amorphous partner. In this regard, vibrational spectroscopy presents a useful tool to analyse these interactions because changes in the molecular arrangement may be reflected in shifts in the vibrations of functional groups involved in such interactions, e.g. hydrogen bonding. However, even with single amorphous compounds this analysis can be challenging because changes are often minor or get lost in the complexity of the spectra. In case of materials with more than one compound, this becomes even more complicated. The purpose of this study was to investigate the molecular near range order of the co-amorphous blend of naproxen (NAP) and indomethacin (IND) (1:1 molar ratio) using quantum mechanical calculations together with FT-infrared (IR) spectroscopy. Initially, both drug molecules were optimized as monomer, homodimer and heterodimer using density functional theory. In a second step the respective IR spectra were calculated. Comparison of the calculated and experimental spectra of the individual drugs revealed that both molecules exist as homodimers in their respective amorphous state. A detailed analysis of the theoretical heterodimer and experimental co-amorphous spectra revealed that the changes of vibrational modes were similar in both, when compared to the single amorphous or homodimer spectra. This indicates that both drugs form a heterodimer when prepared as a co-amorphous 1:1 molar blend.
Keywords: density functional theory, quantum mechanical chemistry, co-amorphous, naproxen-indomethacin, infrared spectroscopy