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Spatial Variation of Pressure in the Lyophilization Product Chamber Part 1: Computational Modeling

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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.

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Acknowledgments

This work was done in collaboration with Cyrus Agarabi, Mansoor Khan, and Rakhi Shah from FDA and is funded by NIPTE-U01-PU002-2012.

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Correspondence to Alina Alexeenko.

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Ganguly, A., Varma, N., Sane, P. et al. Spatial Variation of Pressure in the Lyophilization Product Chamber Part 1: Computational Modeling. AAPS PharmSciTech 18, 577–585 (2017). https://doi.org/10.1208/s12249-016-0513-3

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