title: Spatial Variation of Pressure in the Lyophilization Product Chamber Part 1: Computational Modeling.
abstract: The flow physics in the product chamber of a freeze dryer involves coupled heat and mass transfer at different length and time scales. The low-pressure environment and the relatively small flow velocities make it difficult to quantify the flow structure experimentally. The current work presents the three-dimensional computational fluid dynamics (CFD) modeling for vapor flow in a laboratory scale freeze dryer validated with experimental data and theory. The model accounts for the presence of a non-condensable gas such as nitrogen or air using a continuum multi-species model. The flow structure at different sublimation rates, chamber pressures, and shelf-gaps are systematically investigated. Emphasis has been placed on accurately predicting the pressure variation across the subliming front. At a chamber set pressure of 115 mtorr and a sublimation rate of 1.3 kg/h/m2, the pressure variation reaches about 9 mtorr. The pressure variation increased linearly with sublimation rate in the range of 0.5 to 1.3 kg/h/m2. The dependence of pressure variation on the shelf-gap was also studied both computationally and experimentally. The CFD modeling results are found to agree within 10% with the experimental measurements. The computational model was also compared to analytical solution valid for small shelf-gaps. Thus, the current work presents validation study motivating broader use of CFD in optimizing freeze-drying process and equipment design.
authors.affiliation: School of Aeronautics and Astronautics, Purdue University, 701 W. Stadium Ave, Neil Armstrong Hall, West Lafayette, IN, 47907, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: School of Aeronautics and Astronautics, Purdue University, 701 W. Stadium Ave, Neil Armstrong Hall, West Lafayette, IN, 47907, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Varma
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Sane
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Bogner
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pikal
authors.affiliation: School of Aeronautics and Astronautics, Purdue University, 701 W. Stadium Ave, Neil Armstrong Hall, West Lafayette, IN, 47907, USA. alexeenk@purdue.edu.
authors.forename: Alina
authors.initials: A
authors.lastname: Alexeenko
mesh_terms: D003198:Computer Simulation; D004867:Equipment Design / Q000379:methods*; D005612:Freeze Drying / Q000379:methods*; D006358:Hot Temperature; D008962:Models, Theoretical; D011312:Pressure
keywords: Fluid mechanics; Freeze-drying; Lyophilization; Modeling; Pressure variation; Scale-up