Ph. D. Thesis.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 result