The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA vaccines by converting them into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the progress of freeze-drying techniques for mRNA vaccines, with emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA vaccines and provides a comprehensive overview of the formulation components, including excipients, buffers, and surfactants, as well as the process parameters and storage conditions that aim to improve stability and shelf-life. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA vaccines and enhancing their global accessibility.

The instability of mRNA-LNP vaccines presents significant challenges in storage, transportation, and large-scale distribution, particularly in resource-constrained countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving efficacy and enhancing the long-term stability of mRNA vaccines by converting mRNA-LNP formulations into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the optimization and progress of freeze-drying techniques for mRNA-LNP vaccines, with a particular emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA-LNP vaccines and provides a comprehensive overview of the formulation components like excipients (cryoprotectants and lyoprotectants), buffers, surfactants and also the process parameters, and storage conditions. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA-LNP vaccines and enhancing their global accessibility.