Evaluation of tunable diode laser absorption spectroscopy for in-process water vapor mass flux measurements during freeze drying

  1. Henning Gieseler1,*,
  2. William J. Kessler2,
  3. Michael Finson2,
  4. Steven J. Davis2,
  5. Phillip A. Mulhall2,
  6. Vincent Bons3,
  7. David J. Debo3,
  8. Michael J. Pikal4

Article first published online: 12 JAN 2007

DOI: 10.1002/jps.20827

Issue

Journal of Pharmaceutical Sciences

Journal of Pharmaceutical Sciences

Volume 96, Issue 7, pages 1776–1793, July 2007

Additional Information

How to Cite

Gieseler, H., Kessler, W. J., Finson, M., Davis, S. J., Mulhall, P. A., Bons, V., Debo, D. J. and Pikal, M. J. (2007), Evaluation of tunable diode laser absorption spectroscopy for in-process water vapor mass flux measurements during freeze drying. Journal of Pharmaceutical Sciences, 96: 1776–1793. doi: 10.1002/jps.20827

Author Information

  1. 1

    Department of Pharmaceutics, University of Erlangen, Cauerstrasse 4, 91058 Erlangen, Germany

  2. 2

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

  3. 3

    BOC Edwards Pharmaceutical Systems (BOC EPS), 2175 Military Road, Tonawanda, New York 14150

  4. 4

    School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Storrs, Connecticut 06269

*Department of Pharmaceutics, University of Erlangen, Cauerstrasse 4, 91058 Erlangen, Germany. Telephone: +49 (0)9131-8529556; Fax: +49 (0) 9131-8529545

Publication History

  1. Issue published online: 29 MAY 2007
  2. Article first published online: 12 JAN 2007
  3. Manuscript Accepted: 5 OCT 2006
  4. Manuscript Received: 16 JUN 2006

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Keywords:

  • freeze drying;
  • process analytical technology (PAT);
  • operational qualification (OQ);
  • scale-up;
  • heat and mass transfer in freeze drying;
  • laser technology

Abstract

The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a freeze-dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale freeze dryers. The ratio of “gravimetric/TDLAS” measurements of water removed was 1.02 ± 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the “gravimetric/TDLAS” ratio for the 5% mannitol runs dried in both freeze dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot dryers indicated a higher restriction to mass flow for the lab scale freeze dryer. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1776–1793, 2007

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