T₂ relaxation study to evaluate the crystalline state of indomethacin containing solid dispersions using time-domain NMR

The aim of this study was to demonstrate the usefulness of T₂ measurements conducted with a time-domain NMR (TD-NMR) for the characterization of active pharmaceutical ingredients (APIs) containing solid dosage forms. A solid dispersion (SD) and a physical mixture (PM) consisting of indomethacin (IMC) and polyvinylpyrrolidone (PVP) were prepared at different weight ratios as test samples, and then their T₂ relaxation curves were measured by TD-NMR. The T₂ relaxation curve of IMC was quite different from that of PVP by nature. T₂ values of the SD and PM samples became gradually shortened with increasing IMC content. No difference in T₂ relaxation curves was observed between SD and PM. By analyzing the T₂ relaxation curves in detail, we succeeded in precisely quantifying the IMC contents incorporated in the samples. Next, this study evaluated the T₂ relaxation curves of amorphous and crystalline states of powdered IMC. T₂ relaxation rate of crystalline IMC was slightly but significantly higher than that of amorphous IMC, proving that the T₂ measurement was sensitive enough to detect these differences. Finally, a thermal stress was imposed on SD and PM samples at 60°C for 7d, and then an amorphous-to-crystalline transformation occurred in IMC in the PM sample and was successfully monitored by T₂ measurement. We believe that T₂ measurement by TD-NMR is a promising analysis for the characterization of APIs in solid dosage forms, including SD-based pharmaceuticals.