Quantifying crystalline α-lactose monohydrate in amorphous lactose using terahertz time domain spectroscopy and near infrared spectroscopy

Solveig Warnecke, Jian X. Wu, Åsmund Rinnan*, Morten Allesø, Frans W.J. van den Berg, Peter Uhd Jepsen, Søren Balling Engelsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Spray-dried lactose consists of an amorphous component (10–20%) as well as the crystalline monohydrate form [1]. It is commonly used as a diluent in direct compression, mainly because of its better flow characteristics compared to pure crystalline lactose. The amorphous form is metastable and can relative easily crystallize, which will affect the functionality of the pharmaceutical product. It is therefore of interest to establish methods for non-invasive and rapid assessment of the level of crystallinity in a pharmaceutical formulation. In this study, two spectroscopic methods, near infrared (NIR) spectroscopy and terahertz time domain spectroscopy (THz-TDS), are compared for their ability to determine low levels of crystalline lactose in a mixture. The aim was to find the limit of detection and limit of quantification for the two techniques. Partial least squares (PLS) regression models were developed and the root-mean-square-error-of-cross-validation (RMSECV) for the models with full concentration range were found to be 2.91% (w/w) and 0.87% (w/w) for THz-TDS and NIR, respectively. Calibrations developed on samples containing 0–10% (w/w) crystalline material resulted in RMSECVs of 0.30% (w/w) and 0.20% (w/w) for THz-TDS and NIR, respectively, while the limits of detection were 0.80% (w/w) and 0.43% (w/w), respectively. Both instrumental techniques are thus able to quantify the content of crystalline lactose in a mixture. To select one method over the other in an industrial quality assurance setting, further includes other aspects - such as sample handling, sample size, outlier information, instrument stability, etc. In all these aspects, NIR spectroscopy currently performs better than THz-TDS.
Original languageEnglish
JournalVibrational Spectroscopy
Volume102
Pages (from-to)39-46
ISSN0924-2031
DOIs
Publication statusPublished - 2019

Keywords

  • Terahertz time domain spectroscopy (THz-TDS)
  • NIR
  • Lactose
  • Crystalline
  • Amorphous
  • Limit of detection (LOD)

Cite this

Warnecke, Solveig ; Wu, Jian X. ; Rinnan, Åsmund ; Allesø, Morten ; van den Berg, Frans W.J. ; Jepsen, Peter Uhd ; Engelsen, Søren Balling. / Quantifying crystalline α-lactose monohydrate in amorphous lactose using terahertz time domain spectroscopy and near infrared spectroscopy. In: Vibrational Spectroscopy. 2019 ; Vol. 102. pp. 39-46.
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title = "Quantifying crystalline α-lactose monohydrate in amorphous lactose using terahertz time domain spectroscopy and near infrared spectroscopy",
abstract = "Spray-dried lactose consists of an amorphous component (10–20{\%}) as well as the crystalline monohydrate form [1]. It is commonly used as a diluent in direct compression, mainly because of its better flow characteristics compared to pure crystalline lactose. The amorphous form is metastable and can relative easily crystallize, which will affect the functionality of the pharmaceutical product. It is therefore of interest to establish methods for non-invasive and rapid assessment of the level of crystallinity in a pharmaceutical formulation. In this study, two spectroscopic methods, near infrared (NIR) spectroscopy and terahertz time domain spectroscopy (THz-TDS), are compared for their ability to determine low levels of crystalline lactose in a mixture. The aim was to find the limit of detection and limit of quantification for the two techniques. Partial least squares (PLS) regression models were developed and the root-mean-square-error-of-cross-validation (RMSECV) for the models with full concentration range were found to be 2.91{\%} (w/w) and 0.87{\%} (w/w) for THz-TDS and NIR, respectively. Calibrations developed on samples containing 0–10{\%} (w/w) crystalline material resulted in RMSECVs of 0.30{\%} (w/w) and 0.20{\%} (w/w) for THz-TDS and NIR, respectively, while the limits of detection were 0.80{\%} (w/w) and 0.43{\%} (w/w), respectively. Both instrumental techniques are thus able to quantify the content of crystalline lactose in a mixture. To select one method over the other in an industrial quality assurance setting, further includes other aspects - such as sample handling, sample size, outlier information, instrument stability, etc. In all these aspects, NIR spectroscopy currently performs better than THz-TDS.",
keywords = "Terahertz time domain spectroscopy (THz-TDS), NIR, Lactose, Crystalline, Amorphous, Limit of detection (LOD)",
author = "Solveig Warnecke and Wu, {Jian X.} and {\AA}smund Rinnan and Morten Alles{\o} and {van den Berg}, {Frans W.J.} and Jepsen, {Peter Uhd} and Engelsen, {S{\o}ren Balling}",
year = "2019",
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language = "English",
volume = "102",
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journal = "Vibrational Spectroscopy",
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Quantifying crystalline α-lactose monohydrate in amorphous lactose using terahertz time domain spectroscopy and near infrared spectroscopy. / Warnecke, Solveig; Wu, Jian X.; Rinnan, Åsmund; Allesø, Morten; van den Berg, Frans W.J. ; Jepsen, Peter Uhd; Engelsen, Søren Balling.

In: Vibrational Spectroscopy, Vol. 102, 2019, p. 39-46.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Quantifying crystalline α-lactose monohydrate in amorphous lactose using terahertz time domain spectroscopy and near infrared spectroscopy

AU - Warnecke, Solveig

AU - Wu, Jian X.

AU - Rinnan, Åsmund

AU - Allesø, Morten

AU - van den Berg, Frans W.J.

AU - Jepsen, Peter Uhd

AU - Engelsen, Søren Balling

PY - 2019

Y1 - 2019

N2 - Spray-dried lactose consists of an amorphous component (10–20%) as well as the crystalline monohydrate form [1]. It is commonly used as a diluent in direct compression, mainly because of its better flow characteristics compared to pure crystalline lactose. The amorphous form is metastable and can relative easily crystallize, which will affect the functionality of the pharmaceutical product. It is therefore of interest to establish methods for non-invasive and rapid assessment of the level of crystallinity in a pharmaceutical formulation. In this study, two spectroscopic methods, near infrared (NIR) spectroscopy and terahertz time domain spectroscopy (THz-TDS), are compared for their ability to determine low levels of crystalline lactose in a mixture. The aim was to find the limit of detection and limit of quantification for the two techniques. Partial least squares (PLS) regression models were developed and the root-mean-square-error-of-cross-validation (RMSECV) for the models with full concentration range were found to be 2.91% (w/w) and 0.87% (w/w) for THz-TDS and NIR, respectively. Calibrations developed on samples containing 0–10% (w/w) crystalline material resulted in RMSECVs of 0.30% (w/w) and 0.20% (w/w) for THz-TDS and NIR, respectively, while the limits of detection were 0.80% (w/w) and 0.43% (w/w), respectively. Both instrumental techniques are thus able to quantify the content of crystalline lactose in a mixture. To select one method over the other in an industrial quality assurance setting, further includes other aspects - such as sample handling, sample size, outlier information, instrument stability, etc. In all these aspects, NIR spectroscopy currently performs better than THz-TDS.

AB - Spray-dried lactose consists of an amorphous component (10–20%) as well as the crystalline monohydrate form [1]. It is commonly used as a diluent in direct compression, mainly because of its better flow characteristics compared to pure crystalline lactose. The amorphous form is metastable and can relative easily crystallize, which will affect the functionality of the pharmaceutical product. It is therefore of interest to establish methods for non-invasive and rapid assessment of the level of crystallinity in a pharmaceutical formulation. In this study, two spectroscopic methods, near infrared (NIR) spectroscopy and terahertz time domain spectroscopy (THz-TDS), are compared for their ability to determine low levels of crystalline lactose in a mixture. The aim was to find the limit of detection and limit of quantification for the two techniques. Partial least squares (PLS) regression models were developed and the root-mean-square-error-of-cross-validation (RMSECV) for the models with full concentration range were found to be 2.91% (w/w) and 0.87% (w/w) for THz-TDS and NIR, respectively. Calibrations developed on samples containing 0–10% (w/w) crystalline material resulted in RMSECVs of 0.30% (w/w) and 0.20% (w/w) for THz-TDS and NIR, respectively, while the limits of detection were 0.80% (w/w) and 0.43% (w/w), respectively. Both instrumental techniques are thus able to quantify the content of crystalline lactose in a mixture. To select one method over the other in an industrial quality assurance setting, further includes other aspects - such as sample handling, sample size, outlier information, instrument stability, etc. In all these aspects, NIR spectroscopy currently performs better than THz-TDS.

KW - Terahertz time domain spectroscopy (THz-TDS)

KW - NIR

KW - Lactose

KW - Crystalline

KW - Amorphous

KW - Limit of detection (LOD)

U2 - 10.1016/j.vibspec.2019.03.004

DO - 10.1016/j.vibspec.2019.03.004

M3 - Journal article

VL - 102

SP - 39

EP - 46

JO - Vibrational Spectroscopy

JF - Vibrational Spectroscopy

SN - 0924-2031

ER -