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Keywords:

  • freeze-drying;
  • computational fluid dynamics;
  • vacuum gas dynamics;
  • measurements

Abstract

Analysis of water vapor flows encountered in pharmaceutical freeze-drying systems, laboratory-scale and industrial, is presented based on the computational fluid dynamics (CFD) techniques. The flows under continuum gas conditions are analyzed using the solution of the Navier–Stokes equations whereas the rarefied flow solutions are obtained by the direct simulation Monte Carlo (DSMC) method for the Boltzmann equation. Examples of application of CFD techniques to laboratory-scale and industrial scale freeze-drying processes are discussed with an emphasis on the utility of CFD for improvement of design and experimental characterization of pharmaceutical freeze-drying hardware and processes. The current article presents a two-dimensional simulation of a laboratory scale dryer with an emphasis on the importance of drying conditions and hardware design on process control and a three-dimensional simulation of an industrial dryer containing a comparison of the obtained results with analytical viscous flow solutions. It was found that the presence of clean in place (CIP)/sterilize in place (SIP) piping in the duct lead to significant changes in the flow field characteristics. The simulation results for vapor flow rates in an industrial freeze-dryer have been compared to tunable diode laser absorption spectroscopy (TDLAS) and gravimetric measurements. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3483–3494, 2009