Nondestructive Investigation of the Agglomeration Process for Nanosuspensions via NMR Relaxation of Water Molecules

This study investigated an agglomeration of nanoparticles in a suspension using nuclear magnetic resonance (NMR) relaxation. The nanosuspension was prepared by wet bead milling using indomethacin and polyvinylpyrrolidone as an active pharmaceutical ingredient (API) and stabilizer, respectively. Transmission profiles using a dispersion analyzer based on multilight scattering technology confirmed that agglomeration occurred at 25 °C immediately after wet bead milling. In this study, we focused on the water molecules, not nanoparticles, and obtained the T₂ relaxation time (T₂) of the water molecules using the time-domain NMR (TD-NMR) technique. During the storage period, the T₂ value rapidly increased at the beginning of the storage. In a suspension system, because the T₂ value of water molecules is known to reflect the surface area of the particle, the observed rapid increase in T₂ value indicated an agglomeration of nanoparticles. Therefore, it was shown that the measurement of T₂ relaxation of a nanosuspension could evaluate the agglomeration process. This technique directly observes water molecules as opposed to nanoparticles. Thus, we believe that TD-NMR is a general-purpose technique that is independent of the type of API or polymer.