Sustainable bubble mediated spray-antisolvent crystallization: precise size control and polymorph selection of glycine ultrafine particles.

The traditional antisolvent crystallization often faces issues with uneven particle size distribution when preparing ultrafine crystalline materials. To address this, a sustainable bubble mediated spray-antisolvent crystallization method (BSAC(II)) is proposed, which enables precise control over the particle size and morphology of glycine through interfacial confinement. The method involves driving atomized droplets into the antisolvent body using a vacuum pump, leveraging the dynamic interface of ascending bubbles for rapid solvent exchange and crystallization. Compared to traditional methods, BSAC(II) reduces the glycine particle size from several hundred micrometers to 1-3 μm. Further optimization with antisolvent screens (ethanol, isopropanol, n-propanol) and binary solvent systems (ethanol-water mixtures) reduced the particle size to 700 nm. PXRD analysis confirmed that the mesh induced selective crystallization of metastable α-phase. This method produces glycine ultrafine particles without additives, enhancing their dissolution and dispersion for food industry applications and providing a viable approach for preparing ultrafine food additives.