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 (56nm to 132nm) at higher rates (up to 864gd⁻¹) than many other available technologies. The particle size can be predicted according to the diffusion limited coalescence model ((Formula presented) 0.89) in the slow mixing regime. Molecular weight (between 1kDa to 54kDa) and total flowrate (between 48mLmin⁻¹to 120mLmin⁻¹) had no effect on particle size. We also fit a statistical power-law model ((Formula presented) 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.