Screening for differences in the amorphous state of indomethacin using multivariate visualization
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Screening for differences in the amorphous state of indomethacin using multivariate visualization. / Savolainen, Marja; Heinz, Andrea; Strachan, Clare; Gordon, Keith C.; Yliruusi, Jouko; Rades, Thomas; Sandler, Niklas.
I: European Journal of Pharmaceutical Sciences, Bind 30, Nr. 2, 2007, s. 113-123.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Screening for differences in the amorphous state of indomethacin using multivariate visualization
AU - Savolainen, Marja
AU - Heinz, Andrea
AU - Strachan, Clare
AU - Gordon, Keith C.
AU - Yliruusi, Jouko
AU - Rades, Thomas
AU - Sandler, Niklas
PY - 2007
Y1 - 2007
N2 - The aim of this study was to examine molecular-level differences in the amorphous state of indomethacin prepared from both alpha- and gamma-polymorphs using various preparative techniques: milling, quench cooling of a melt, slow cooling of a melt and spray drying. X-ray powder diffraction (XRPD), polarizing light microscopy (PLM), differential scanning calorimetry, as well as mid-infrared (MIR), near infrared (NIR) and Raman spectroscopy were used to analyze the samples after preparation. Principal component analysis (PCA) was used to visualize the differences in the spectroscopic data. According to the XRPD and PLM measurements, all samples except the spray dried indomethacin were amorphous after preparation. Spray dried indomethacin had some remaining residual crystallinity. Differences in the amorphous samples could be found on molecular level: the milled samples clustered separately from the other amorphous samples in the PCA of MIR, NIR and Raman spectra. This could be due to either small degrees of undetected crystallinity remaining in the samples after milling or differences in the hydrogen bonding in the different amorphous samples of indomethacin. The spectroscopic techniques revealed different information about the samples. Raman spectroscopy was most sensitive to differences caused by the preparation techniques and degradation products. Multivariate methods, such as PCA, offer an efficient tool to screen for these differences in the amorphous state.
AB - The aim of this study was to examine molecular-level differences in the amorphous state of indomethacin prepared from both alpha- and gamma-polymorphs using various preparative techniques: milling, quench cooling of a melt, slow cooling of a melt and spray drying. X-ray powder diffraction (XRPD), polarizing light microscopy (PLM), differential scanning calorimetry, as well as mid-infrared (MIR), near infrared (NIR) and Raman spectroscopy were used to analyze the samples after preparation. Principal component analysis (PCA) was used to visualize the differences in the spectroscopic data. According to the XRPD and PLM measurements, all samples except the spray dried indomethacin were amorphous after preparation. Spray dried indomethacin had some remaining residual crystallinity. Differences in the amorphous samples could be found on molecular level: the milled samples clustered separately from the other amorphous samples in the PCA of MIR, NIR and Raman spectra. This could be due to either small degrees of undetected crystallinity remaining in the samples after milling or differences in the hydrogen bonding in the different amorphous samples of indomethacin. The spectroscopic techniques revealed different information about the samples. Raman spectroscopy was most sensitive to differences caused by the preparation techniques and degradation products. Multivariate methods, such as PCA, offer an efficient tool to screen for these differences in the amorphous state.
KW - indomethacin
KW - amorphous state
KW - principal component analysis
KW - spectroscopic techniques
U2 - 10.1016/j.ejps.2006.10.010
DO - 10.1016/j.ejps.2006.10.010
M3 - Journal article
C2 - 17169536
VL - 30
SP - 113
EP - 123
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
SN - 0928-0987
IS - 2
ER -
ID: 40357231