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

被引:13
作者
Ganguly, Arnab [1 ]
Varma, Nikhil [1 ]
Sane, Pooja [2 ]
Bogner, Robin [2 ]
Pikal, Michael [2 ]
Alexeenko, Alina [1 ]
机构
[1] Purdue Univ, Sch Aeronaut & Astronaut, 701 W Stadium Ave,Neil Armstrong Hall, W Lafayette, IN 47907 USA
[2] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA
来源
AAPS PHARMSCITECH | 2017年 / 18卷 / 03期
关键词
Fluid mechanics; Freeze-drying; Lyophilization; Modeling; Pressure variation; Scale-up;
D O I
10.1208/s12249-016-0513-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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/m(2), 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/m(2). 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.
引用
收藏
页码:577 / 585
页数:9
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