Quantitative Evaluation of the Crystallinity of Indomethacin Using ¹H T₂ Relaxation Behaviors Measured by Time Domain NMR

We sought to demonstrate the usefulness of the T₂ relaxation behaviors measured by time domain NMR (TD-NMR) for the quantitative evaluation of the crystallinity of an active pharmaceutical ingredient (API). This study used indomethacin as a model API. After blending amorphous and crystalline indomethacin powders at a designated ratio, T₂ relaxation curves were measured by TD-NMR. Subsequently, we acquired a calibration curve to quantify crystallinity by curve fitting analysis. Validation demonstrated a good correlation between the theoretical and experimental percentage of crystallinity. Thus, this study succeeded in a precise estimation of crystallinity of indomethacin using TD-NMR. We also investigated whether the technique is practical by testing indomethacin powders with unknown proportion of crystallinity, and then compared their estimated crystallinity with that found using conventional evaluation techniques. The quantitative performance of the TD-NMR technique was comparable to that of Raman spectroscopy. Furthermore, indomethacin powder blended with excipients, which can be used to produce tablets, was tested. The TD-NMR technique was still able to quantify the crystallinity of indomethacin, even when excipients were incorporated into the sample. Therefore, the present study expands the horizon for evaluating the crystallinity of APIs in pharmaceutical sciences.