Continuous production of drug nanocrystals by porous hollow fiber-based anti-solvent crystallization

Abstract Nanotechnology is being utilized to develop advanced concepts in drug delivery systems including production of nanodrugs such as, nanocrystals and nanosuspensions. Continuous crystallization methods are of increasing interest and porous hollow fiber membrane (HFM) based modules have been recently utilized as an anti-solvent crystallizer. The porous hollow fiber anti-solvent crystallizer (PHFAC) based method has been modified here to produce continuously nanocrystals of Griseofulvin (GF). In the PHFAC device, deionized water introduced from the HFM bore into the shell side is used as the anti-solvent; acetone containing dissolved GF is introduced into the shell side of the HFM module as the drug solution. Water, the anti-solvent, mixed vigorously with the drug solution leading to drug crystallization and the drug crystals were separated by vacuum filtration and freeze-dried. The experimental conditions were varied to control the particle size, size distribution and the appearance of the nanoparticles. The properties of the drug nanocrystals were characterized via Transmission Electron Microscopy (TEM), Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS), Raman Spectroscopy, Energy Dispersive X-rays Spectroscopy (EDX), Differential Scanning Calorimetry (DSC), FT-IR Spectrometer, X-ray Diffraction (XRD); drug dissolution tests were also implemented. Drug nanocrystals as small as 86.4 nm were produced under modest pressure and temperature conditions in a controllable and continuous manner.