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In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools

Thomas De Beer UGent, Pieter Vercruysse UGent, Anneleen Burggraeve UGent, Thomas Quinten UGent, J. Ouyang, X. Zhang, Chris Vervaet UGent, Jean Paul Remon UGent and Willy Baeyens UGent (2009) Journal of Pharmaceutical Sciences. 98(9). p.3430-3446
abstract
The aim of the present study was to examine the complementary properties of Raman and near infrared (NIR) spectroscopy as PAT tools for the fast, noninvasive, non-destructive and in-line process monitoring of a freeze drying process. Therefore, Raman and NIR probes were built in the freeze dryer chamber, allowing simultaneous process monitoring. A 5% (w/v) mannitol solution was used as model for freeze drying. Raman and NIR spectra were continuously collected during freeze drying (one Raman and NIR spectrum/min) and the spectra were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR). Raman spectroscopy was able to supply information about (i) the mannitol solid state throughout the entire process, (ii) the endpoint of freezing (endpoint of mannitol crystallization), and (iii) several physical and chemical phenomena occurring during the process (onset of ice nucleation, onset of mannitol crystallization). NIR spectroscopy proved to be a more sensitive tool to monitor the critical aspects during drying: (i) endpoint of ice sublimation and (ii) monitoring the release of hydrate water during storage. Furthermore, via NIR spectroscopy some Raman observations were confirmed: start of ice nucleation, end of mannitol crystallization and solid state characteristics of the end product. When Raman and NIR monitoring were performed on the same vial, the Raman signal was saturated during the freezing step caused by reflected NIR light reaching the Raman detector. Therefore, NIR and Raman measurements were done on a different vial. Also the importance of the position of the probes (Raman probe above the vial and NIR probe at the bottom of the sidewall of the vial) in order to obtain all required critical information is outlined. Combining Raman and NIR spectroscopy for the simultaneous monitoring of freeze drying allows monitoring almost all critical freeze drying process aspects. Both techniques do not only complement each other, they also provided mutual confirmation of specific conclusions.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CRYSTALLIZATION, LYOPHILIZATION, D-MANNITOL, CURVE RESOLUTION, MANOMETRIC TEMPERATURE-MEASUREMENT, NEAR-INFRARED SPECTROSCOPY, multivariate curve resolution (MCR), principal component analysis (PCA), process monitoring, freeze drying, NIR spectroscopy, process analytical technology (PAT), Raman spectroscopy, DIFFERENTIATION, CHEMOMETRICS, MIXTURES, MOISTURE
journal title
Journal of Pharmaceutical Sciences
J. Pharm. Sci.
volume
98
issue
9
pages
3430 - 3446
publisher
John Wiley & Sons
Web of Science type
Article
Web of Science id
000269569200040
JCR category
CHEMISTRY, MULTIDISCIPLINARY
JCR impact factor
2.906 (2009)
JCR rank
34/137 (2009)
JCR quartile
1 (2009)
ISSN
0022-3549
DOI
10.1002/jps.21633
language
English
UGent publication?
yes
classification
A1
copyright statement
I don't know the status of the copyright for this publication
id
761512
handle
http://hdl.handle.net/1854/LU-761512
date created
2009-10-07 14:27:49
date last changed
2009-11-06 09:05:23
@article{761512,
  abstract     = {The aim of the present study was to examine the complementary properties of Raman and near infrared (NIR) spectroscopy as PAT tools for the fast, noninvasive, non-destructive and in-line process monitoring of a freeze drying process. Therefore, Raman and NIR probes were built in the freeze dryer chamber, allowing simultaneous process monitoring. A 5\% (w/v) mannitol solution was used as model for freeze drying. Raman and NIR spectra were continuously collected during freeze drying (one Raman and NIR spectrum/min) and the spectra were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR). Raman spectroscopy was able to supply information about (i) the mannitol solid state throughout the entire process, (ii) the endpoint of freezing (endpoint of mannitol crystallization), and (iii) several physical and chemical phenomena occurring during the process (onset of ice nucleation, onset of mannitol crystallization). NIR spectroscopy proved to be a more sensitive tool to monitor the critical aspects during drying: (i) endpoint of ice sublimation and (ii) monitoring the release of hydrate water during storage. Furthermore, via NIR spectroscopy some Raman observations were confirmed: start of ice nucleation, end of mannitol crystallization and solid state characteristics of the end product. When Raman and NIR monitoring were performed on the same vial, the Raman signal was saturated during the freezing step caused by reflected NIR light reaching the Raman detector. Therefore, NIR and Raman measurements were done on a different vial. Also the importance of the position of the probes (Raman probe above the vial and NIR probe at the bottom of the sidewall of the vial) in order to obtain all required critical information is outlined. Combining Raman and NIR spectroscopy for the simultaneous monitoring of freeze drying allows monitoring almost all critical freeze drying process aspects. Both techniques do not only complement each other, they also provided mutual confirmation of specific conclusions.},
  author       = {De Beer, Thomas and Vercruysse, Pieter and Burggraeve, Anneleen and Quinten, Thomas and Ouyang, J. and Zhang, X. and Vervaet, Chris and Remon, Jean Paul and Baeyens, Willy},
  issn         = {0022-3549},
  journal      = {Journal of Pharmaceutical Sciences},
  keyword      = {CRYSTALLIZATION,LYOPHILIZATION,D-MANNITOL,CURVE RESOLUTION,MANOMETRIC TEMPERATURE-MEASUREMENT,NEAR-INFRARED SPECTROSCOPY,multivariate curve resolution (MCR),principal component analysis (PCA),process monitoring,freeze drying,NIR spectroscopy,process analytical technology (PAT),Raman spectroscopy,DIFFERENTIATION,CHEMOMETRICS,MIXTURES,MOISTURE},
  language     = {eng},
  number       = {9},
  pages        = {3430--3446},
  publisher    = {John Wiley \& Sons},
  title        = {In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools},
  url          = {http://dx.doi.org/10.1002/jps.21633},
  volume       = {98},
  year         = {2009},
}

Chicago
De Beer, Thomas, Pieter Vercruysse, Anneleen Burggraeve, Thomas Quinten, J. Ouyang, X. Zhang, Chris Vervaet, Jean Paul Remon, and Willy Baeyens. 2009. “In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools.” Journal of Pharmaceutical Sciences 98 (9): 3430–3446.
APA
De Beer, T., Vercruysse, P., Burggraeve, A., Quinten, T., Ouyang, J., Zhang, X., Vervaet, C., et al. (2009). In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools. Journal of Pharmaceutical Sciences, 98(9), 3430–3446.
Vancouver
1.
De Beer T, Vercruysse P, Burggraeve A, Quinten T, Ouyang J, Zhang X, et al. In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools. Journal of Pharmaceutical Sciences. John Wiley & Sons; 2009;98(9):3430–46.
MLA
De Beer, Thomas, Pieter Vercruysse, Anneleen Burggraeve, et al. “In-Line and Real-Time Process Monitoring of a Freeze Drying Process Using Raman and NIR Spectroscopy as Complementary Process Analytical Technology (PAT) Tools.” Journal of Pharmaceutical Sciences 98.9 (2009): 3430–3446. Print.