Continuous production of polymer coated drug crystals, submicron particles, and nanoparticles by hollow fiber membrane-based cooling and anti-solvent crystallization

Currently, no technique is available to continuously film coat fine and nano-sized drug particles with a polymer to produce large amounts of free-flowing coated particles. We have adapted both the solid hollow fiber cooling crystallization (SHFCC) and the porous hollow fiber membrane-based anti-solvent crystallization (PHFAC) techniques to continuously produce polymer-coated micro-particles, nanoparticles, and drug crystals. Controlled cooling or addition of an anti-solvent allows for polymer nucleation on the surface of the particles and the formation of a thin polymer film around the particles, the thickness of which can be varied depending on the operating conditions. Furthermore, scale-up of both techniques can be easily accomplished by using a larger SHFCC or PHFAC module containing a larger number of solid or porous hollow fiber membranes (HFMs).