Use of Time-Domain NMR for ¹H T₁ Relaxation Measurement and Fitting Analysis in Homogeneity Evaluation of Amorphous Solid Dispersion

This study examined the usefulness of ¹H T₁ relaxation measurements for evaluating the homogeneity of amorphous solid dispersion (ASD). Indomethacin and polyvinylpyrrolidone were used to prepare two kinds of ASDs. One was inhomogeneous ASD (ASD_melt) prepared by a melt-quenching method, and the other was homogeneous ASD (ASD_solvent) prepared by a solvent evaporation method. The T₁ relaxation was measured by the time-domain NMR (TD-NMR) technique using a low-field NMR system. Curve-fitting analysis of T₁ relaxation plots was conducted using the Akaike information criterion. This fitting analysis revealed that the T₁ relaxation of ASD_melt and ASD_solvent was biphasic and monophasic, respectively. ASD_melt and ASD_solvent were inhomogeneous and homogeneous on a nanometer scale, respectively, considering the spin diffusion of ¹H nuclei. These T₁ results were consistent with the Raman mapping of ASDs. From the fitting analysis of ¹H T₁ relaxation, we conclude that TD-NMR is a promising technique for evaluating ASD homogeneity.