Continuous nanoprecipitation of poly(D,L-lactide) in a rotor–stator spinning disk reactor

The demand for polymeric nanoparticles is increasing as more and more studies showcase the efficacy of nano-sized drug delivery systems. However, current technologies struggle to produce these nanoparticles on a scale sufficiently large for clinical trials or industry. We have developed a continuous nanoprecipitation process for poly(D,L-lactide) in a rotor–stator spinning disk reactor that produces uniform (dispersity < 0.2) nanoparticles (56 nm to 132 nm) at higher rates (up to 864 g d −1 ) than many other available technologies. The particle size can be predicted according to the diffusion limited coalescence model ( R 2 = 0.89) in the slow mixing regime. Molecular weight (between 1 kDa to 54 kDa) and total flowrate (between 48 mL min −1 to 120 mL min −1 ) had no effect on particle size. We also fit a statistical power-law model ( R 2 = 0.88) that predicts particle size in relation to the experimental parameters (concentration of polymer in the aqueous phase, rotational speed, flowrate ratio between the organic and aqueous phase). Polymer concentration in the organic phase and disk rotation are the dominant factors influencing size while the flowrate ratio has one-third their impact. • A rotor–stator spinning disk reactor produced polymeric particles as small as 56 nm. • Particle dispersity ranged from 0.10 to 0.22. • Polymer concentration and disk rotation determined particle size. • Nanoparticles can be produced at a rate of 0.8 kg/day. • Drug loading of ibuprofen in polylactic acid nanoparticles peaked at 6 %.