Small-angle neutron scattering for characterization of pharmaceutical formulations

Small-angle neutron scattering (SANS) is a non-destructive structural characterization technique based on neutron-matter interactions, capable of providing microstructural information at the nanometer to micrometer scale (1-1 000 nm), including particle size distribution, morphological features, internal phase structures, and intermolecular interactions in pharmaceutical formulations. With the rapid development of nanodrug delivery systems (e.g., liposomes, polymeric micelles, lipid nanoparticles) and biologics (e.g., monoclonal antibodies, mRNA vaccines), conventional characterization techniques (e.g., electron microscopy, dynamic light scattering) face limitations in analyzing complex drug systems. Owing to its high sensitivity to light elements, exceptional penetration depth, and isotope discrimination capability, SANS offers unique advantages for probing the microstructure of pharmaceutical formulations. This review systematically summarizes recent advances in SANS applications for drug characterization, focusing on its pivotal role in elucidating the structure of nanodrug carriers, monitoring conformational dynamics of biologics, and investigating the self-assembly behavior of active pharmaceutical ingredients (APIs). Furthermore, the challenges of SANS in sample preparation, data analysis, and facility accessibility are discussed, along with future perspectives on integrating SANS with emerging technologies such as artificial intelligence and multiscale modeling. This review aims to provide new insights and technical support for the rational design and performance optimization of advanced drug formulations.