Spray Freeze Drying for Solid Formulations of RNA Lipid Nanoparticles

Spray-freeze drying (SFD) is a promising drying technique for stabilizing RNA lipid nanoparticles (RNA-LNPs) by converting them into solid-state formulations. This study examined the impact of the SFD process and the widely utilized stabilizing disaccharides, such as sucrose and trehalose, on the major properties (e.g. particle size, encapsulation efficiency) of RNA-LNPs post drying. Various process parameters, such as atomization, freezing, and drying temperature, were systematically evaluated, along with the impact of incorporating annealing post freezing step. Surface area measurements, solid-state particle size analysis, scanning electron microscopy, powder X-ray diffraction and solid-state NMR spectroscopy were employed to gain deeper insights into powder characteristics and matrix mobility. Our findings demonstrated that sucrose provided superior stabilization as compared to trehalose in our tested formulations and processes. Moreover, incorporation of the annealing process enhanced LNP stability. Results from the stability study revealed that the annealed 10% and 20% sucrose formulations maintained their stability, highlighting the potential of optimized SFD processing for producing solid formulations of RNA-LNPs.