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Hydrate formation during wet granulation studied by spectroscopic methods and multivariate analysis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Anna Jørgensen
  • Rantanen, Jukka
  • Milja Karjalainen
  • Leonid Khriachtchev
  • Eetu Räsänen
  • Jouko Yliruusi

PURPOSE: The aim was to follow hydrate formation of two structurally related drugs, theophylline and caffeine, during wet granulation using fast and nondestructive spectroscopic methods.

METHODS: Anhydrous theophylline and caffeine were granulated with purified water. Charge-coupled device (CCD) Raman spectroscopy was compared with near-infrared spectroscopy (NIR) in following hydrate formation of drugs during wet granulation (off-line). To perform an at-line process analysis, the effect of water addition was monitored by NIR spectroscopy and principal components analysis (PCA). The changes in the crystal arrangements were verified by using X-ray powder diffraction (XRPD).

RESULTS: Hydrate formation of theophylline and caffeine could be followed by CCD Raman spectroscopy. The NIR and Raman spectroscopic results were consistent with each other. NIR revealed the state of water, and Raman spectroscopy gave information related to the drug molecule itself. The XRPD confirmed the spectroscopic results. PCA with three principal components explained 99.9 of the spectral variation in the second derivative NIR spectra.

CONCLUSIONS: Both CCD Raman and NIR spectroscopic methods can be applied to monitoring of hydrate formation processes. However, NIR is more suitable for monitoring solid-water interactions.

OriginalsprogEngelsk
TidsskriftPharmaceutical Research
Vol/bind19
Udgave nummer9
Sider (fra-til)1285-91
Antal sider7
ISSN0724-8741
StatusUdgivet - sep. 2002

    Forskningsområder

  • Multivariate Analysis, Spectrum Analysis, Raman, Technology, Pharmaceutical, Wettability, Wetting Agents

ID: 140623049