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A Compact Model for Lyophilizer Equipment Capability Estimation

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Abstract

This work presents a compact model for the equipment capability limit of a common configuration of pharmaceutical lyophilizers, a product chamber separated from the condenser by a duct and isolation valve, at a wide range of design parameters. The equipment capability limit is one of the most important characteristics determining the lyophilization design space for a particular product, container, and equipment combination. Experimental measurements of equipment capability are time-consuming and expensive, especially at the production scale. Numerical modeling using computational fluid dynamics may reduce the number of experiments and provide insights into the physics of the process with high resolution. The computational fluid dynamics (CFD) modeling has been used in this work to develop a compact model for lyophilizer equipment capability. This eliminates the need for end users to create a full CFD model of the equipment and process. Full CFD and compact model simulations for laboratory and pilot-scale lyophilizers have been compared with tunable diode laser absorption spectroscopy measurements of the water vapor mass flow during ice slab tests. The compact model results average deviation from the experimental data is within 10%, whereas the full CFD simulations are within 5%. The compact model is based on several key parameters which are the main characteristics of a lyophilizer affecting the equipment capability curve. These parameters are discussed, and their effect on the modeling results is shown.

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Acknowledgements

The authors would like to thank ANSYS for providing Fluent research licenses.

Funding

Funding for this project was provided by the National Institute for Innovation in Manufacturing Biologicals (NIIMBL) under grant #70NANB17H002. Support for the development of the pilot-scale freeze-drying facility was provided by the Massachusetts Life Sciences Center (MLSC), NIIMBL, and UML.

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Authors and Affiliations

  1. School of Aeronautics and Astronautics, Purdue University, West Lafayette, Indiana, 47907, USA

    Petr Kazarin & Alina Alexeenko

  2. Birck Nanotechnology Center, Purdue University, 1205 W State St., West Lafayette, Indiana, 47907, USA

    Petr Kazarin

  3. Physical Science Inc., Andover, Massachusetts, 01810, USA

    William Kessler & Emily Gong

  4. Francis College of Engineering, University of Massachusetts Lowell, Lowell, Massachusetts, 01854, USA

    Seongkyu Yoon, Huolong Liu & Richard Marx

  5. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269, USA

    Robin Bogner

  6. Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana, 47907, USA

    Alina Alexeenko

Authors
  1. Petr Kazarin
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  2. William Kessler
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  3. Emily Gong
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  4. Seongkyu Yoon
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  5. Huolong Liu
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  6. Richard Marx
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  7. Robin Bogner
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  8. Alina Alexeenko
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Contributions

Petr Kazarin: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Accountable for the work and end to end.

William Kessler: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Emily Gong: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Seongkyu Yoon: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Huolong Liu: responsible for conducting the experiments, providing the experimental data and its analysis; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Richard Marx: responsible for conducting the experiments, providing the experimental data and its analysis; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Robin Bogner: responsible for revising the work critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Alina Alexeenko: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Accountable for the work and end to end.

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Correspondence to Petr Kazarin.

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Kazarin, P., Kessler, W., Gong, E. et al. A Compact Model for Lyophilizer Equipment Capability Estimation. AAPS PharmSciTech 23, 14 (2022). https://doi.org/10.1208/s12249-021-02167-8

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