Comparison of pharmaceutical formulations: ATR-FTIR spectroscopic imaging to study drug-carrier interactions

Attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopic imaging has been used in combination with UV detection to study the release of a model poorly water-soluble drug, indomethacin, when formulated with selected drug carriers. Firstly, formulations of indomethacin and nicotinamide in varying weight ratios were studied since novel tablet dosage forms containing multi-drugs are of industrial interest. The in situ spectroscopic imaging measurements of the dissolving tablets showed that as the loading of indomethacin was increased, the rate of drug release changed from one that expressed first-order drug release to one which showed zero-order drug release. Two drug release mechanisms have been identified from the recorded spectroscopic images and UV dissolution profiles. To further validate these mechanisms, specific formulations containing the model drug and two other excipients, urea and mannitol, were studied. The formulations with urea showed similar first-order release, indicative of the drug-carrier interactions. Whereas, the indomethacin/mannitol formulations showed a zero-order release curve explained by disintegration of the tablet. ATR-FTIR spectroscopic imaging provided highly chemically specific information as well as the spatial distribution of the components during the dissolution process which has demonstrated the potential of this combined analytical setup to determine the mechanisms of drug release.