Quantification of process induced disorder in milled samples using different analytical techniques

Research output: Contribution to journalJournal articlepeer-review

Standard

Quantification of process induced disorder in milled samples using different analytical techniques. / Zimper, Ulrike; Aaltonen, Jaakko; McGoverin, Cushla M.; Gordon, Keith C.; Krauel-Goellner, Karen; Rades, Thomas.

In: Pharmaceutics, Vol. 2, No. 1, 28.08.2012, p. 30-49.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Zimper, U, Aaltonen, J, McGoverin, CM, Gordon, KC, Krauel-Goellner, K & Rades, T 2012, 'Quantification of process induced disorder in milled samples using different analytical techniques', Pharmaceutics, vol. 2, no. 1, pp. 30-49. <https://www.mdpi.com/1999-4923/2/1/30>

APA

Zimper, U., Aaltonen, J., McGoverin, C. M., Gordon, K. C., Krauel-Goellner, K., & Rades, T. (2012). Quantification of process induced disorder in milled samples using different analytical techniques. Pharmaceutics, 2(1), 30-49. https://www.mdpi.com/1999-4923/2/1/30

Vancouver

Zimper U, Aaltonen J, McGoverin CM, Gordon KC, Krauel-Goellner K, Rades T. Quantification of process induced disorder in milled samples using different analytical techniques. Pharmaceutics. 2012 Aug 28;2(1):30-49.

Author

Zimper, Ulrike ; Aaltonen, Jaakko ; McGoverin, Cushla M. ; Gordon, Keith C. ; Krauel-Goellner, Karen ; Rades, Thomas. / Quantification of process induced disorder in milled samples using different analytical techniques. In: Pharmaceutics. 2012 ; Vol. 2, No. 1. pp. 30-49.

Bibtex

@article{8c502122af914ae899a26686dbe12b10,
title = "Quantification of process induced disorder in milled samples using different analytical techniques",
abstract = "The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected.",
keywords = "biology, chemistry",
author = "Ulrike Zimper and Jaakko Aaltonen and McGoverin, {Cushla M.} and Gordon, {Keith C.} and Karen Krauel-Goellner and Thomas Rades",
year = "2012",
month = aug,
day = "28",
language = "English",
volume = "2",
pages = "30--49",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "1",

}

RIS

TY - JOUR

T1 - Quantification of process induced disorder in milled samples using different analytical techniques

AU - Zimper, Ulrike

AU - Aaltonen, Jaakko

AU - McGoverin, Cushla M.

AU - Gordon, Keith C.

AU - Krauel-Goellner, Karen

AU - Rades, Thomas

PY - 2012/8/28

Y1 - 2012/8/28

N2 - The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected.

AB - The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected.

KW - biology

KW - chemistry

M3 - Journal article

VL - 2

SP - 30

EP - 49

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

ER -

ID: 40380833