Pore network modeling of freeze drying on the basis of lyomicroscopic and tomographic measurements

• Applicants: Professorin Dr.-Ing. Petra Först; Professor Dr.-Ing. Evangelos Tsotsas
• Subject Area: Mechanical Process Engineering ; Chemical and Thermal Process Engineering
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413284489

• Final Report Year: 2023

Final Report Abstract

Freeze-drying is a process commonly required to produce and stabilize high-quality products, but it is also slow, expensive and energy-intensive because it takes place at temperatures and pressures below the triple point of water. Attempts to increase efficiency quickly bring the process into ranges where product damage can occur. This is characterized by local softening of the frozen solid and is also referred to as structural collapse. The collapse is caused by local effects that take place on microscopic structures of the material. They are experimentally accessible only with great effort and cannot be described with the mathematical models established for freeze-drying. Moreover, they cannot be predicted so far. The project therefore aimed to develop, for the first time, a mathematical model for freeze-drying that can capture the phenomena on the scale of single pores, i.e. on the micrometer scale. This goal was realized using a so-called pore network model (PNM). PNMs are discrete mathematical models with which mass and heat exchange between individual pores can be calculated and represented. In the project, the pore network structure was accurately reconstructed based on data from 3-dimensional imaging. Experimental data, for example on the temperature or pressure profile during the process, were also necessary to complete the model. To record these and other necessary process parameters, a freeze-drying cell and imaging techniques were developed in order to visualize the sublimation of water 3-dimensionally in addition to the thermodynamic quantities mentioned above. The pore structure was resolved at the same time. With the experimental setup, the progress of drying can now be quantified much more precisely, which is essential for comparison with the model data and further development of the model. The new method of imaging and computer simulation can serve as a basis for future model adaptations, with which the local events that lead to damage of the pore structure at demanding process conditions, i.e. close to the collapse, can be quantified.

Publications

• Application of neutron radiography and tomography for the investigation of freeze drying, In: Proceedings of the European Drying Conference (EuroDrying), Torino, Italy, July 10-12, 2019.
  Vorhauer, N.; Först, P.; Hilmer, M.; Mannes, D. & Tsotsas, E.
  
• Characterization of primary lyophilization of frozen bulky solids, In: Proceedings of Partec, Nürnberg, Germany, April 9-11, 2019.
  Först, P.; Vorhauer, N. & Tsotsas, E.
  
• Neutron imaging of freeze drying as a starting point for the development of new mathematical models, MLZ Annual Report, Garching, Germany, 2019.
  Gruber, S.; Vorhauer, N.; Schulz, M.; Hilmer, M.; Peters, J.; Tsotsas, E. & Först, P.
  
• Characterization of Lyophilization of Frozen Bulky Solids. Chemical Engineering & Technology, 43(5), 789-796.
  Foerst, Petra; Gruber, Sebastian; Schulz, Michael; Vorhauer, Nicole & Tsotsas, Evangelos
  
• Development of a Freeze-Drying Stage for In-Situ µ-CT Measurements. Processes, 8(7), 869.
  Hilmer, Mathias; Gruber, Sebastian & Foerst, Petra
  
• Estimation of the local sublimation front velocities from neutron radiography and tomography of particulate matter. Chemical Engineering Science, 211, 115268.
  Gruber, S.; Vorhauer, N.; Schulz, M.; Hilmer, M.; Peters, J.; Tsotsas, E. & Foerst, P.
  
• Freeze-Drying with Structured Sublimation Fronts—Visualization with Neutron Imaging. Processes, 8(9), 1091.
  Vorhauer-Huget, Nicole; Mannes, David; Hilmer, Mathias; Gruber, Sebastian; Strobl, Markus; Tsotsas, Evangelos & Foerst, Petra
  
• Beschreibung der Sublimationsfront in Schüttgütern mittels Neutronenradiographie und - tomographie, Die Pharmazeutische Industrie 2021, 83, 694-704.
  Gruber, S.; Vorhauer-Huget, N.; Schulz, M.; Hilmer, M.; Peters, J.; Tsotsas, E. & Foerst, P.
  
• Determination of 3D pore network structure of freeze-dried maltodextrin. Drying Technology, 40(4), 748-766.
  Thomik, M.; Gruber, S.; Foerst, P.; Tsotsas, E. & Vorhauer-Huget, N.
  
• In situ micro-computed tomography to study microstructure and sublimation front during freeze-drying. Food Structure, 29, 100213.
  Gruber, S.; Vorhauer-Huget, N. & Foerst, P.
  
• Evaluation of methods to represent the structure in tomographic images of freeze-dried porous media. Proceedings of the 22nd International Drying Symposium on Drying Technology -IDS '22. Worcester Polytechnic Institute -Gordon Library.
  Briest, Lucas; Vorhauer, Nicole; Gruber, Sebastian; Petra, Först; Schuchmann, Harald & Tsotsas, Evangelos
  
• Experimental investigations on freeze-drying of particulate matter by using neutron imaging. Proceedings of the 22nd International Drying Symposium on Drying Technology -IDS '22. Worcester Polytechnic Institute -Gordon Library.
  Vorhauer, Nicole; Schulz, Michael; Xu, Xinjing; Hilmer, Mathias; Thomik, Maximilian; Tsotsas, Evangelos; Schuchmann, Harald & Foerst, Petra
  
• Experimental Study of the Impact of Pore Structure on Drying Kinetics and Sublimation Front Patterns. Pharmaceutics, 14(8), 1538.
  Thomik, Maximilian; Gruber, Sebastian; Kaestner, Anders; Foerst, Petra; Tsotsas, Evangelos & Vorhauer-Huget, Nicole
  
• The Influence of Local Microstructure Inhomogeneities on Local Drying Kinetics during Freeze-Drying. Pharmaceutics, 14(10), 2132.
  Gruber, Sebastian; Thomik, Maximilian; Vorhauer-Huget, Nicole; Hans, Lukas; Tsotsas, Evangelos & Foerst, Petra
  
• Use of advanced imaging techniques as a valuable tool to analyze the freeze-drying process in more detail, Interpore, Online, May 31 - June 2, 2022.
  Gruber, S.; Thomik, M.; Vorhauer-Huget, N.; Coppens, F.; Tsotsas, E. & Foerst, P.
  
• A Non-Isothermal Pore Network Model of Primary Freeze Drying. Pharmaceutics, 15(8), 2131.
  Thomik, Maximilian; Faber, Felix; Gruber, Sebastian; Foerst, Petra; Tsotsas, Evangelos & Vorhauer-Huget, Nicole
  
• In-situ analysis of the 3-D microstructure and its impact on the freeze-drying kinetics, In: Proceedings of the European Drying Conference (EuroDrying), Lodz, Polen, July 4-7, 2023.
  Gruber, S.; Thomik, M.; Coppens, F.; Vorhauer-Huget, N.; Tsotsas, E. & Foerst, P.
  
• Pore network simulation of heat and mass Transfer during freeze-drying of porous media, In: Proceedings of the European Drying Conference (EuroDrying), Lodz, Polen, July 4-7, 2023.
  Vorhauer-Huget, N.; Thomik, M.; Gruber, S.; Foerst, P. & Tsotsas, E.
  
• Pore Scale Investigation of Freeze-Drying. Album of Porous Media, 114-114. Springer International Publishing.
  Gruber, Sebastian; Foerst, Petra; Thomik, Maximilian; Tsotsas, Evangelos & Vorhauer-Huget, Nicole
  
• Using 4D-Imaging to describe the impact of the microstructure on sublimation front patterns, Interpore, Edinburgh, Scotland, May 22-25, 2023.
  Gruber, S.; Thomik, M.; Coppens, F.; Vorhauer-Huget, N.; Tsotsas, E. & Foerst, P.