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Characterisation of indomethacin and nifedipine using variable-temperature solid-state NMR
David C Apperley1, Angus H Forster, Romain Fournier
1Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK.
Magnetic Resonance in Chemistry : MRC
|August 2, 2005
Summary
This study uses solid-state NMR to characterize crystalline and amorphous forms of indomethacin and nifedipine, revealing differences in their stability and recrystallization behavior relevant to drug formulation.
Area of Science:
- Solid-state chemistry
- Pharmaceutical sciences
- Materials science
Background:
- Polymorphism significantly impacts drug properties, including solubility, stability, and bioavailability.
- Understanding the behavior of amorphous drug forms is crucial for developing stable pharmaceutical formulations.
- Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for characterizing molecular structure and dynamics.
Purpose of the Study:
- To characterize the stable polymorphic forms of indomethacin and nifedipine using solid-state NMR.
- To investigate the molecular dynamics and glass transition behavior of amorphous indomethacin and nifedipine.
- To compare the real-time stability and recrystallization tendencies of the crystalline and amorphous states of these drugs.
Main Methods:
- 13C Cross-Polarization Magic Angle Spinning (CPMAS) NMR spectroscopy to assign resonances and study polymorphic forms.
- Variable-temperature 1H NMR relaxation measurements (T1rho and T1) to probe molecular motion and glass transitions.
- Proton bandshape measurements to monitor recrystallization processes.
- Supporting techniques: Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-Transform Infrared (FTIR) spectroscopy, and solution-state NMR.
Main Results:
- NMR assignments were made for crystalline indomethacin and nifedipine.
- Variable-temperature studies revealed distinct molecular motions and glass transition behaviors (Tg) for amorphous indomethacin and nifedipine.
- Nifedipine exhibited lower real-time stability in its amorphous form compared to indomethacin, evidenced by earlier recrystallization onset and behavior upon crushing.
- Recrystallization of nifedipine was detected at lower temperatures (70°C) than indomethacin (110°C).
Conclusions:
- Solid-state NMR provides valuable insights into the polymorphic characterization and stability of drug molecules.
- Differences in molecular dynamics and glass transition behavior correlate with the observed real-time stabilities of amorphous indomethacin and nifedipine.
- The findings have implications for the selection and formulation of stable solid forms for these pharmaceutical compounds.