Factors affecting flash nanoprecipitation of Pharmaceuticals: Principles and applications

Flash nanoprecipitation (FNP) has emerged as a transformative technique in the preparation of nanoparticles for targeted drug delivery. Traditional drug delivery systems often struggle with challenges such as poor solubility, limited bioavailability, and suboptimal targeting. FNP addresses these limitations through a one-step, scalable process that produces nanoparticles with tunable size, composition, morphology, and surface characteristics. This review explores the principles of FNP, focusing on its application in encapsulating bioactive agents, achieving controlled release, and enhancing bioavailability. Unlike conventional emulsification or antisolvent precipitation methods, FNP utilizes rapid mixing under kinetically controlled conditions to achieve high reproducibility and uniform particle distribution. The technique has been successfully employed for various pharmaceutical applications, including the delivery of small molecules, biologics, and nucleic acids. Beyond laboratory research, FNP has been adopted in industrial and clinical settings-for instance, in the scalable production of lipid nanoparticles (LNPs) for mRNA-based vaccines and other nucleic acid therapeutics-demonstrating its translational potential. Furthermore, its adaptability extends to theranostic and imaging applications. The review highlights critical formulation variables and process parameters, such as polymer type and its glass transition temperature, solvent selection, and Reynolds number, which influence key characteristics such as nanoparticle stability and performance. By synthesizing recent advances, this paper provides a comprehensive overview of how FNP is already transforming drug delivery, highlighting its current impact, and future research directions.