Continuous synthesis of drug nanocrystals by solid hollow fiber cooling crystallization

Int J Pharm. 2020 Feb 25;576:118978. doi: 10.1016/j.ijpharm.2019.118978. Epub 2019 Dec 20.


Size reduction of drug with poor water solubility to nanoscale is an effective way to help improve the efficacy of drug delivery to the human body. A solid hollow fiber cooling crystallization technique has been adopted to continuously produce griseofulvin drug nanoparticles under modest conditions with accurate controllability. In the solid hollow fiber cooling crystallization device, drug solution flowed through the bores of solid hollow fibers while the cooling liquid was circulated counter-currently in the shell side of the device to cool down the drug solution in the tube side. Due to intense heat exchange between the cooling liquid and the drug solution through the thin fiber walls, the temperature of drug solution decreased rapidly so that drug nanoparticles were precipitated out from the solution by sudden reduction of solubility. Through variation of the experimental conditions and parameters, the mean size of the produced nanoparticles was regulated and controlled. The nanoparticles were dispersed uniformly, the chemical structure and bonds of prepared nanoparticles was the same with as-received griseofulvin. Both raw material and NPs the polymorph(s) present form I, the melting point was 220 °C. Drug dissolution testing was also executed to verify that nanocrystals have a higher dissolution profile.

Keywords: Drug nanoparticles; Griseofulvin; Precipitation; Solid hollow fibers cooling crystallization.

MeSH terms

  • Crystallization / methods*
  • Drug Delivery Systems / methods
  • Griseofulvin / chemistry
  • Nanoparticles / chemistry*
  • Particle Size
  • Solubility
  • Solvents / chemistry
  • Temperature


  • Solvents
  • Griseofulvin