Aerosol synthesis of lipid nanoparticles: relating crystallinity to simulated evaporation rate

Abstract

The degree of crystallinity of nanometer size lipid matrices governs drug loading and release rates. Recently, droplet-phase aerosol synthesis was used to prepare lipid nanoparticles of stearic acid and achieve control over their crystallinity using precursor solvents with differing vapor pressures. The present work aims at examining relationships between solvent evaporation rate and extent of evaporative cooling, during drop evaporation, on the crystallinity of the resulting lipid nanoparticles. A stationary drop model was developed to study evaporation of submicron-sized solution drops, of stearic acid in organic solvents, by including mechanisms of solvent vapor pressure depression by the solute, heat and mass transfer between the drop ensemble and suspending gas, Kelvin (curvature) effect, noncontinuum vapor transfer effects, and changes in activity coefficients of solute and solvent with changing concentrations. It was found that increasing estimated evaporation rates correlated with decreasing measured crystallinity. Higher evaporation rates also led to greater evaporative cooling and lower drop temperatures. The rate of change of supersaturation in solution drops under fast evaporation was shown to be an order of magnitude higher than that for slow evaporation. The modeled evaporation rate and drop temperature depend primarily on vapor pressure and enthalpy of vaporization of the precursor solvent. This suggests that selection of precursor solvents, with desired physical properties, can be used to control crystallinity, and related drug release behavior of lipid nanoparticles made through aerosol synthesis routes.