Vaporization and particle formation during drying of multisolvent droplet without and with antisolvent-vapor infusion

Abstract

The understanding of the evaporation-drying of multi-solvent-solute containing droplets was advanced with a unique single droplet drying (SDD) approach. Analyzing the drying of dual-solvent droplets revealed two stages of temperature increase and the alteration of solute precipitation behavior, from at droplet surface to at the interior of droplet. When a single-solvent droplet was dried with antisolvent vapor, droplet temperature remained constant along the precipitated solids forming microparticles, despite the simultaneous evaporation of original solvent and antisolvent. Toluene and water droplets during ethanol-vapor-infused drying at 31 °C reached the same constant temperature of 27.5 °C, namely the free-evaporating temperature of ethanol. Mathematical and chromatography analyses showed that the solvent composition kept changing. The changing rate, governed by antisolvent vapor density, could profoundly impact final particle morphology, producing lactose microparticles with five distinct morphologies. The proposed SDD technique enables coupled analyses of drying kinetics and microstructure formation for elucidating complex in-drying mechanisms.