Solid-state nuclear magnetic resonance spectroscopy (NMR) is a powerful analytical tool that is used to characterize materials in several different fields including catalysis, batteries, and pharmaceuticals. While solid-state NMR is a powerful analytical tool that provides structural information at the molecular level, it may require long experimental times due to unfavorable relaxation properties, low gyromagnetic ratios, and low natural abundances of nuclei of interest (e.g., 13C and 15N). One alternative to performing solid-state NMR for the analysis of pharmaceuticals is to use time domain NMR (TD-NMR) using a simple benchtop spectrometer. The TD-NMR instrument offers several advantages over traditional solid-state NMR including lower operating cost, a smaller footprint and an entry level scientist can operate/ interpret the data. One specific application of TD-NMR spectroscopy in the pharmaceutical industry is the analysis of lyophilized protein sugar matrices. TD-NMR has the potential for inline analysis of samples to determine their miscibility. Unlike solid-state NMR, which requires packing the sample into an NMR rotor and breaking apart the lyophilized cake, TD-NMR is nondestructive and noninvasive, being able to measure the intact lyophilized sample in its container. As a proof of concept, the 1H T1 relaxation times were measured using the TD-NMR (B0(1H) = 20MHz) and traditional solid-state NMR (B0(1H) = 400 MHz) for lyophilized human serum albumin (HSA) / sucrose matrices, where the protein to sugar ratio was varied. The same trend for the 1H T1 of lyophilized HSA / sucrose samples was observed on both the TD-NMR and high field NMR. As the sucrose to protein ratio was increased, the 1H T1 increased as well. Previous research has shown that the longer 1H T1 value correlates with increased stability. This proof of concept shows that TD-NMR can provide higher throughput of analysis compared to traditional solid-state NMR testing.
