Although the importance of miscibility in ensuring protein stability is recognized, there are limited studies to evaluate the impact of excipients and processes in the inhomogeneity of solid protein formulations. This is mostly due to the lack of a high-resolution technique that can identify and quantify the mixing of protein and excipient. Common miscibility/homogeneity characterization techniques like DSC and X-ray diffraction (XRD) can identify inhomogeneity in the solid formulation, but their sensitivity can be insufficient to monitor inhomogeneity at a smaller scale in the solid protein formulations. The traditional high-resolution surface imaging techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM) can achieve the nanoscale resolution often necessary for miscibility evaluations. However, these techniques are not able to identify the chemical compositions of different phases. With more advanced x-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (TOF-SIMs) surface characterization, which enables the chemical composition characterization of the excipient atoms with nitrogen might interfere with protein quantification. The typical sub-surface imaging using spectroscopic techniques such as fluorescent spectroscopy, IR, and Raman spectroscopy, provides component distribution, but low image resolution and low depth penetration. ssNMR has been implemented as an advanced and high-resolution tool to assess the molecular mixing of bulk powder samples at sub-100-nm resolution in amorphous solid dispersions (ASDs). Going beyond the applications of small molecule formulations, ssNMR also offers high resolution to identify phase separation in glassy protein formulations. The 1 H ssNMR spin-lattice relaxation measurements were typically used to evaluate the miscibility of protein-sugar lyophilizates, illustrated by the three scenarios in Figure . NMR relaxation values in the laboratory (T1) and rotating frame (T1ρ) represent the averaged properties of multiple nearby nuclei due to homonuclear 1 H spin diffusion. Relaxation parameters on different time scales can be used to evaluate spin diffusion over different length scales. 1 H T1 is typically ranging from 1-10s, corresponding to a spin diffusion over ~ 20-200nm, while 1 H T1ρ is from 1-10ms, estimates spin diffusion over ~ 1-20 nm length scale. The miscibility between sugar and protein can be identified on a 1-10 and a 20-200 nm length scale respectively through the relaxation time comparison. It was applied to understand the impact of the molecular weight of sugar on the miscibility and corresponding storage stability of IgG after lyophilization. Smaller sugars like trehalose provide better miscibility with IgG on both small and large scales, whereas the largest protein dextran 70 kDa performed worst and phase separation was observed on both scales. The miscibility behavior correlates with protein storage stability. Smaller sugar trehalose demonstrated better miscibility as a lower tendency of aggregation during storage and vice versa for larger sugars. Further, Chen et al. have recently utilized ssNMR to investigate the impact of protein-excipient interaction and miscibility on the physical stability of spray-dried protein formulation. The data suggest substantial immiscibility and phase separation between BSA and Leucine which leads to a poor stabilization effect. In contrast, trehalose showed the best storage stability in spraydried BSA solids as trehalose remains amorphous and is miscible at both 1-20 and 20-200 nm scale. Buffer salt is the most common excipient used in the protein formulation to retain the appropriate pH and buffering capacity. Mutukuri et al. examined the effect of buffer salts on the physical stability of BSA from both spray-dried and lyophilized formulations. 208 ssNMR effectively identified the presence of phase separation between the succinic salt and the BSA in the lyophilized formulation. This phase separation results in a loss of long-term stability. Similarly, Tower et al. utilized ssNMR to measure homogeneity on 20-50 and 1-3 nm domains and mobility related to β-relaxation of HSA with trehalose or sucrose lyophilized solid. The trehalose crystallization at higher trehalose to HSA ratio resulted in sample inhomogeneity by differences in the 1 H T1 and 1 H T1ρ relaxation time values. In addition, a 1 H T1 relaxation time shorter than 1.5 s indicates an unstable sample under the given stability conditions and ssNMR acquisition parameters.