A practical time-domain nuclear magnetic resonance-based method for empirical assessment of homogeneity in amorphous solid dispersions.

Amorphous solid dispersion (ASD) is a widely used formulation strategy for enhancing the solubility of poorly water-soluble drugs; however, ensuring sufficient drug-polymer miscibility remains a practical challenge because microscopic inhomogeneity can accelerate crystallization and undermine product quality. Although nuclear magnetic resonance (NMR) relaxation has been explored as a nondestructive tool for characterizing ASD structure, its application has primarily been limited to qualitative assessments. This study develops a practical empirical approach using fitting-error indices to compare ASD homogeneity using time-domain NMR (TD-NMR) with a low-field benchtop instrument. First, two model ASDs of probucol and polyvinylpyrrolidone with distinct homogeneity levels were prepared, and their microscopic homogeneity was subsequently compared using error indices derived from monoexponential fitting of 1H T1 relaxation. Second, to assess applicability under realistic storage conditions, humidified storage was used to induce phase separation and crystallization, and the ability of TD-NMR to monitor these changes was assessed. The TD-NMR results were consistent with powder X-ray diffraction and modulated differential scanning calorimetry measurements. These findings suggest that TD-NMR provides a rapid, nondestructive, and practical tool for empirically monitoring homogeneity-related changes and structural deterioration in ASD powders.