A Simple, Organic Solvent-Free, and Scalable Process for Producing Calcium Alginate Nanoparticle Powder by High-Pressure Homogenization and Spray Drying.

Scaling up nanoparticle production remains one of the main bottlenecks for translating laboratory formulations into industrially relevant processes. This study established an organic solvent-free and reproducible process to produce calcium alginate nanoparticles by integrating ionic gelation, high-pressure homogenization, and spray drying. Scale-up of the synthesis step was demonstrated by increasing the ionic gelation batch volume from 400 mL to 2 L, while high-pressure homogenization at 1000 bar was subsequently applied as a refining step, reducing particle size from the micrometer range to approximately 223 nm at 400 mL scale and 236 nm at 2 L scale. The spray-dried powders exhibited low water activity, stable morphology, and a predominantly amorphous structure, as indicated by SEM, TEM, XRD, XRF, and thermal analyses. The integrated workflow yielded nanoparticles with structural integrity and controlled physicochemical properties, supporting the potential of this platform for future studies involving encapsulation systems and related technological applications.