Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses

Int J Pharm. 2015 Dec 30;496(1):75-85. doi: 10.1016/j.ijpharm.2015.05.025. Epub 2015 May 14.


Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its impact on total drying time. Five different formulations, each having a different dry cake resistance, were tested. After freezing, the traditionally frozen vials were placed on the shelves while the spin-frozen vials were placed in aluminum vial holders providing radial energy supply during drying. Different primary drying conditions and chamber pressures were evaluated. After 2h of primary drying, the amount of sublimed ice was determined in each vial. Each formulation was monitored in-line using NIR spectroscopy during drying to determine the sublimation endpoint and the influence of drying conditions upon total drying time. For all tested formulations and applied freeze-drying conditions, there was a significant higher sublimation rate in the spin-frozen vials. This can be explained by the larger product surface and the lower importance of product resistance because of the much thinner product layers in the spin frozen vials. The in-line NIR measurements allowed evaluating the influence of applied drying conditions on the drying trajectories.

Keywords: Continuous freeze drying; Freeze-drying; NIR spectroscopy; Spin freezing.

Publication types

  • Comparative Study

MeSH terms

  • Chemistry, Pharmaceutical / methods*
  • Drug Compounding / methods*
  • Excipients / chemistry*
  • Freeze Drying
  • Freezing
  • Spectroscopy, Near-Infrared / methods
  • Technology, Pharmaceutical / methods*


  • Excipients