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Development of a Mini-Freeze Dryer for Material-Sparing Laboratory Processing with Representative Product Temperature History

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Abstract

The goal of the work described in this publication was to evaluate a new, small, material-sparing freeze dryer, denoted as the “mini-freeze dryer or mini-FD”, capable of reproducing the product temperature history of larger freeze dryers, thereby facilitating scale-up. The mini-FD wall temperatures can be controlled to mimic loading procedures and dryer process characteristics of larger dryers. The mini-FD is equipped with a tunable diode laser absorption spectroscopy (TDLAS) water vapor mass flow monitor and with other advanced process analytical technology (PAT) sensors. Drying experiments were performed to demonstrate scalability to larger freeze dryers, including the determination of vial heat transfer coefficients, K v . Product temperature histories during K v runs were evaluated and compared with those obtained with a commercial laboratory-scale freeze dryer (LyoStar II) for sucrose and mannitol product formulations. When the mini-FD wall temperature was set at the LyoStar II band temperature (− 20°C) to mimic lab dryer edge vials, edge vial drying in the mini-FD possessed an average K v within 5% of those obtained during drying in the LyoStar II. When the wall temperature of the mini-FD was set equal to the central vial product temperature, edge vials behaved as center vials, possessing a K v value within 5% of those measured in the LyoStar II. During both K v runs and complete product freeze drying runs, the temperature-time profiles for the average edge vials and central vial in the mini-FD agreed well with the average edge and average central vials of the LyoStar II.

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Notes

  1. This practice is intended to expose the mini-freeze dryer edge vial to additional heat transfer equivalent to that experienced by the edge vial in a tray. While this is expected to be a good approximation, it is not exact as some of the edge vials in a tray in a lab or production dryer nearly touch the band, thereby allowing for some gas-phase heat transfer, which is absent in the mini-freeze dryer. In addition, some of the vials are exposed directly to the wall of the freeze dryer, which runs warmer than the band. Alternately, and likely better, one could employ a circular “band” in the mini-FD and then use a wall temperature equivalent to the wall temperature found in the larger-scale dryer of interest. This was employed during a subset of experiments performed using the beta mini-freeze dryer.

  2. Previous experience with standard gravimetric K v determinations using the LyoStar indicates that the normal standard deviation for replicate measurement is about 5% in K v , meaning that a difference between single K v values (i.e., for a given vial number) would be expected to have a standard deviation of about 7% and the difference between a single value and an average of 6 (edge vial comparison) would have a standard deviation of slightly more than 5%.

  3. The LyoCalculator is a pseudo steady-state mass and heat transfer model for estimating the impact of changes in process conditions on the product temperature history in primary drying. It runs on an excel spreadsheet that will be made available to interested parties.

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Acknowledgements

UConn and PSI scientists thank SP Scientific (Warminster, PA) for their support in developing the alpha and beta prototype Mini-FD. Authors also acknowledge the support of Jordan University of Science and Technology/Jordan.

Funding

The work described in this presentation was supported by award number HHSN261201300092C from the National Institutes of Health and National Cancer Institute.

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Authors and Affiliations

  1. Jordan University of Science and Technology, Irbid, Jordan

    Wasfy M. Obeidat

  2. Injectable Drug Product Technology Services, Pfizer, Inc., McPherson, Kansas, USA

    Ekneet Sahni

  3. Physical Sciences Inc., 20 New England Business Center, Andover, Massachusetts, 01810, USA

    William Kessler

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

    Michael Pikal

Authors
  1. Wasfy M. Obeidat
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  2. Ekneet Sahni
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  3. William Kessler
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  4. Michael Pikal
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Corresponding author

Correspondence to Wasfy M. Obeidat.

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The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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The authors declare that they have no conflicts of interest.

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Obeidat, W.M., Sahni, E., Kessler, W. et al. Development of a Mini-Freeze Dryer for Material-Sparing Laboratory Processing with Representative Product Temperature History. AAPS PharmSciTech 19, 599–609 (2018). https://doi.org/10.1208/s12249-017-0871-5

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  • DOI: https://doi.org/10.1208/s12249-017-0871-5

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