Process intensification: an integrated nanoparticle formation scheme based on Flash NanoPrecipitation

R.K. Prud’homme, V. Kumar, M. Akbulut, S. D’Addio
Princeton University, US

Keywords: nanoparticle, process intensification, scale up, precipitation

Summary:

There has been significant interest in nanoparticles driven by applications in drug delivery, diagnostics, and imaging. The ultimate success of nanoparticle drug delivery depends upon the ability to translate often elaborate and difficult laboratory processes, which usually involve multiple batch steps, into large scale, reproducible, economically viable processes. Our focus has been on “ultra fast” precipitations that involve two components: (1) rapid micromixing in novel confined impinging jet mixing geometries 1 to effect high supersaturation and nucleation rates, and (2) novel block copolymer stabilizers. The process which we term “Flash NanoPrecipitation” depends critically on three time scales: particle nucleation and growth, block copolymer micellization, and polymer adsorption on the particle to produce steric stabilization. The process is intrinsically scalable and can be run in the laboratory with samples as small as 3 mg of drug while the same apparatus can produce 3 kg of drug/day, and the process has been commercialized to 1400 kg/day. The physics involved in particle self-assembly will be examined for several compounds we have studied. An integrated process that involves particle formation using confined impinging jet reactors, flash evaporation for solvent removal2, and a novel hydrogen bonding precipitation step for particle concentration and drying provides a continuous, scalable, and economic process for nanoparticle formation and isolation. The engineering analysis of the solvent removal and concentration steps will be presented.