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

Abstract

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 (ASDmelt) prepared by a melt-quenching method, and the other was homogeneous ASD (ASDsolvent) 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 ASDmelt and ASDsolvent was biphasic and monophasic, respectively. ASDmelt and ASDsolvent 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.