Experimental and modelling studies of process intensification for the solvent-antisolvent precipitation of nanoparticles in a spinning disc reactor

Abstract

Solvent-antisolvent precipitation is a key process in pharmaceuticals industries. This research concerns solvent-antisolvent precipitation of starch nanoparticles in the spinning disc reactor (SDR), based on a combination of both experimental and modelling studies. The SDR’s ability to use surface rotation to improve micromixing within thin liquid films, as well as its capability to exhibit near plug flow characteristics is the primary motivation to investigate this process intensification technology for solvent-antisolvent precipitation. One of the objectives of this study is to highlight and understand interactions of the disc surface topography with conditions such as flowrate, solvent-antisolvent ratio and disc speed and their impact on the mixing and precipitation processes. Smaller nanoparticles with narrow particle size distributions (PSDs) were produced as flow rate increased from 6 to 18 mL/s (248 to 175 nm) and disc speed increased from 400 to 1200 rpm (234 to 175 nm). This is attributed to increased shear and instabilities within the liquid film, enhancing mixing as the liquid travels outwards on the disc surface. Increasing the antisolvent to solvent ratio from 1:1 to 9:1 also caused a reduction in size (276 to 175 nm), as greater supersaturation was generated at reduced solubilities, causing nucleation to dominate over particle growth. The disc texture did not significantly affect nanoparticle size; however, particles produced on the grooved disc were of narrower PSD with higher yields. Nucleation rates were determined for the precipitation of starch nanoparticles in the SDR. Nucleation rates increased with an increase in flow rate and disc speed but were a weak function of antisolvent to solvent ratio. The nucleation rate was greater on the grooved surface at the poorer precipitation conditions, as the precipitation then relied primarily on better mixing through the eddies generated by the grooved surface. A maximum nucleation rate of 6.44x1016 mL-1 s -1 was estimated at conditions of 1200 rpm, 9:1 ratio and 15 mL/s, on the smooth disc. Finally, experimentally obtained nucleation kinetics along with growth kinetics have been applied to formulate a predictive PSD model, combining the population balance equations (PBE) with a micromixing model. The model uses Hounslow’s discretisation method to solve the PBEs, accounting for nucleation, growth, and agglomeration in the SDR. Validation of the simulated PSDs has been done through comparison against experimental results. The modelled PSDs are in good agreement with the experimental results