Validation of a multipoint near-infrared spectroscopy method for in-line moisture content analysis during freeze-drying

A Kauppinen (Corresponding Author), Maunu Toiviainen, M Lehtonen, K Järvinen, Janne Paaso, Mikko Juuti, J Ketolainen

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)

Abstract

This study assessed the validity of a multipoint near-infrared (NIR) spectroscopy method for in-line moisture content analysis during a freeze-drying process. It is known that the moisture content affects the stability of a freeze-dried product and hence it is a major critical quality attribute. Therefore assessment of the validity of an analytical method for moisture content determination is vital to ensure the quality of the final product. An aqueous sucrose solution was used as the model formulation of the study. The NIR spectra were calibrated to the moisture content using partial least squares (PLS) regression with coulometric Karl Fischer (KF) titration as the reference method. Different spectral preprocessing methods were compared for the PLS models. A calibration model transfer protocol was established to enable the use of the method in the multipoint mode. The accuracy profile was used as a decision tool to determine the validity of the method. The final PLS model, in which NIR spectra were preprocessed with standard normal variate transformation (SNV), resulted in low root mean square error of prediction value of 0.04%-m/v, i.e. evidence of sufficient overall accuracy of the model. The validation results revealed that the accuracy of the model was acceptable within the moisture content range 0.16-0.70%-m/v that is specific for the latter stages of the freeze-drying process. In addition, the results demonstrated the method's reliable in-process performance and robustness. Thus, the multipoint NIR spectroscopy method was proved capable of providing in-line evaluation of moisture content and it is readily available for use in laboratory scale freeze-drying research and development.
Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume95
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

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Near infrared spectroscopy
Near-Infrared Spectroscopy
Freeze Drying
Drying
Moisture
Least-Squares Analysis
Infrared radiation
Titration
Mean square error
Sucrose
Calibration
Research

Keywords

  • Accuracy profile
  • freeze-drying
  • moisture
  • multipoint near-infrared spectroscopy
  • validation

Cite this

Kauppinen, A ; Toiviainen, Maunu ; Lehtonen, M ; Järvinen, K ; Paaso, Janne ; Juuti, Mikko ; Ketolainen, J. / Validation of a multipoint near-infrared spectroscopy method for in-line moisture content analysis during freeze-drying. In: Journal of Pharmaceutical and Biomedical Analysis. 2014 ; Vol. 95. pp. 229-237.
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abstract = "This study assessed the validity of a multipoint near-infrared (NIR) spectroscopy method for in-line moisture content analysis during a freeze-drying process. It is known that the moisture content affects the stability of a freeze-dried product and hence it is a major critical quality attribute. Therefore assessment of the validity of an analytical method for moisture content determination is vital to ensure the quality of the final product. An aqueous sucrose solution was used as the model formulation of the study. The NIR spectra were calibrated to the moisture content using partial least squares (PLS) regression with coulometric Karl Fischer (KF) titration as the reference method. Different spectral preprocessing methods were compared for the PLS models. A calibration model transfer protocol was established to enable the use of the method in the multipoint mode. The accuracy profile was used as a decision tool to determine the validity of the method. The final PLS model, in which NIR spectra were preprocessed with standard normal variate transformation (SNV), resulted in low root mean square error of prediction value of 0.04{\%}-m/v, i.e. evidence of sufficient overall accuracy of the model. The validation results revealed that the accuracy of the model was acceptable within the moisture content range 0.16-0.70{\%}-m/v that is specific for the latter stages of the freeze-drying process. In addition, the results demonstrated the method's reliable in-process performance and robustness. Thus, the multipoint NIR spectroscopy method was proved capable of providing in-line evaluation of moisture content and it is readily available for use in laboratory scale freeze-drying research and development.",
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Validation of a multipoint near-infrared spectroscopy method for in-line moisture content analysis during freeze-drying. / Kauppinen, A (Corresponding Author); Toiviainen, Maunu; Lehtonen, M; Järvinen, K; Paaso, Janne; Juuti, Mikko; Ketolainen, J.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 95, 2014, p. 229-237.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Validation of a multipoint near-infrared spectroscopy method for in-line moisture content analysis during freeze-drying

AU - Kauppinen, A

AU - Toiviainen, Maunu

AU - Lehtonen, M

AU - Järvinen, K

AU - Paaso, Janne

AU - Juuti, Mikko

AU - Ketolainen, J

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N2 - This study assessed the validity of a multipoint near-infrared (NIR) spectroscopy method for in-line moisture content analysis during a freeze-drying process. It is known that the moisture content affects the stability of a freeze-dried product and hence it is a major critical quality attribute. Therefore assessment of the validity of an analytical method for moisture content determination is vital to ensure the quality of the final product. An aqueous sucrose solution was used as the model formulation of the study. The NIR spectra were calibrated to the moisture content using partial least squares (PLS) regression with coulometric Karl Fischer (KF) titration as the reference method. Different spectral preprocessing methods were compared for the PLS models. A calibration model transfer protocol was established to enable the use of the method in the multipoint mode. The accuracy profile was used as a decision tool to determine the validity of the method. The final PLS model, in which NIR spectra were preprocessed with standard normal variate transformation (SNV), resulted in low root mean square error of prediction value of 0.04%-m/v, i.e. evidence of sufficient overall accuracy of the model. The validation results revealed that the accuracy of the model was acceptable within the moisture content range 0.16-0.70%-m/v that is specific for the latter stages of the freeze-drying process. In addition, the results demonstrated the method's reliable in-process performance and robustness. Thus, the multipoint NIR spectroscopy method was proved capable of providing in-line evaluation of moisture content and it is readily available for use in laboratory scale freeze-drying research and development.

AB - This study assessed the validity of a multipoint near-infrared (NIR) spectroscopy method for in-line moisture content analysis during a freeze-drying process. It is known that the moisture content affects the stability of a freeze-dried product and hence it is a major critical quality attribute. Therefore assessment of the validity of an analytical method for moisture content determination is vital to ensure the quality of the final product. An aqueous sucrose solution was used as the model formulation of the study. The NIR spectra were calibrated to the moisture content using partial least squares (PLS) regression with coulometric Karl Fischer (KF) titration as the reference method. Different spectral preprocessing methods were compared for the PLS models. A calibration model transfer protocol was established to enable the use of the method in the multipoint mode. The accuracy profile was used as a decision tool to determine the validity of the method. The final PLS model, in which NIR spectra were preprocessed with standard normal variate transformation (SNV), resulted in low root mean square error of prediction value of 0.04%-m/v, i.e. evidence of sufficient overall accuracy of the model. The validation results revealed that the accuracy of the model was acceptable within the moisture content range 0.16-0.70%-m/v that is specific for the latter stages of the freeze-drying process. In addition, the results demonstrated the method's reliable in-process performance and robustness. Thus, the multipoint NIR spectroscopy method was proved capable of providing in-line evaluation of moisture content and it is readily available for use in laboratory scale freeze-drying research and development.

KW - Accuracy profile

KW - freeze-drying

KW - moisture

KW - multipoint near-infrared spectroscopy

KW - validation

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DO - 10.1016/j.jpba.2014.03.008

M3 - Article

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EP - 237

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -