A case study of real-time monitoring of solid-state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy

Sönke Rehder, Jian-Xiong Wu, Julian Laackmann, Hans-Ulrich Moritz, Jukka Rantanen, Thomas Rades, Claudia S Leopold

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    Abstract

    The objective of this study was to monitor the amorphous-to-crystalline solid-state phase transformation kinetics of the model drug ibuprofen with spectroscopic methods during acoustic levitation. Chemical and physical information was obtained by real-time near infrared (NIRS) and Raman spectroscopy measurements. The recrystallisation kinetic parameters (overall recrystallisation rate constant ß and the time needed to reach 50% of the equilibrated level t(50)), were determined using a multivariate curve resolution approach. The acoustic levitation device coupled with non-invasive spectroscopy enabled monitoring of the recrystallisation process of the difficult-to-handle (adhesive) amorphous sample. The application of multivariate curve resolution enabled isolation of the underlying pure spectra, which corresponded well with the reference spectra of amorphous and crystalline ibuprofen. The recrystallisation kinetic parameters were estimated from the recrystallisation profiles. While the empirical recrystallisation rate constant determined by NIR and Raman spectroscopy were comparable, the lag time for recrystallisation was significantly lower with Raman spectroscopy as compared to NIRS. This observation was explained by the high energy density of the Raman laser beam, which might have led to local heating effects of the sample and thus reduced the recrystallisation onset time. It was concluded that acoustic levitation with NIR and Raman spectroscopy combined with multivariate curve resolution allowed direct determination of the recrystallisation kinetics of amorphous drugs and thus is a promising technique for monitoring solid-state phase transformations of adhesive small-sized samples during the early phase of drug development.
    Original languageEnglish
    JournalEuropean Journal of Pharmaceutical Sciences
    Volume48
    Issue number1-2
    Pages (from-to)97-103
    Number of pages7
    ISSN0928-0987
    DOIs
    Publication statusPublished - 2013

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