Air-jet atomization for preparation of lipid nanoparticles: Dependence of size on solute concentration

Abstract

Engineering nanoparticles for applications such as drug delivery, needs understanding of dependence of particle size on process and precursor parameters. The size of nanoparticles prepared through the aerosol route using solution droplet drying technique is traditionally governed by a 1/3rd scaling law between dry particle diameter and precursor solute concentration. Here, we experimentally investigate this relationship, for precursor solutions of lipids in organic solvents. Nanoparticles were prepared using air-jet atomization of precursor solutions of stearic acid in organic solvents (acetone, chloroform, methanol and ethanol), in a pulse heat aerosol reactor, at a process temperature of 50 °C. The relationship between median mobility diameter of prepared nanoparticles (40–155 nm) and solute concentration was governed by a scaling law exponent (SLE) in the range 0.104–0.182. The observed exponents showed significant deviations from the classical 1/3rd law. The experimental investigation indicated an unexpected increase in particle number concentration with increasing solute concentration for all solvents studied. Simulations with a critical super saturation based solute diffusion model and theoretical calculations of size dependent external factors such as coagulation and wall losses during transit, could not explain the deviation in SLE, nor the increased number concentrations. These considerations point to possible effects of solute concentration on the mechanism of droplet formation during the atomization process. A preliminary model based on an area conservation law has been proposed to explain the twin effects of deviation in SLE and increased droplet number concentration with increasing solute concentration. The present study provides empirical data on the relationship between dry particle diameter and solute concentration in the selected lipid-organic solvent systems. Also, it opens avenues for further understanding nanoparticle formation by air-jet atomization.