Abstract: Spherical silica particles have been synthesised from sodium silicate (Na2SiO3) via flame-assisted spray-drying. The parameters of colloidal properties, such as pH and concentration of a solution (ranging 8–11 and 0.1–0.3 mol/L, respectively), were studied to understand their effects on droplet size and the resultant morphological changes in the silica particles. A three-dimensional multiphase computational fluid dynamic (CFD) simulation for the flame-assisted spray-drying process has been developed to predict the temperature distribution in flame reactors and the generated average particle size. The pH and concentration of the solutions were found to affect the precursor physical properties, such as density, viscosity, and surface tension. This observation was validated by the presence of non-spherical doughnut-like particles using the colloidal precursor at pH 8 and solution concentration 0.1 mol/L. An approach that permits the direct estimation of the average droplet size produced from an ultrasonic nebulizer is presented in this paper. Good agreement, with an approximately 5% negative discrepancy, was observed between the experimental results and the theoretical values. A higher discrepancy of approximately 33% occurred in the particles using the colloidal precursor at pH 8 owing to morphological changes in the silica particles.