Solid-state 13C NMR study of indomethacin polymorphism.

Area of Science:

• Solid-state chemistry
• Materials science
• Pharmaceutical science

Background:

• Indomethacin exists in multiple crystalline forms, including meta-stable alpha and stable gamma.
• Understanding the solid-state packing of these polymorphs is crucial for drug formulation and stability.
• Differences in crystal lattice conformation can impact physicochemical properties.

Purpose of the Study:

• To investigate the molecular conformation differences between the alpha and gamma forms of indomethacin.
• To utilize solid-state (13)C NMR spectroscopy to differentiate these polymorphs.
• To correlate spectral patterns with crystal lattice packing.

Main Methods:

• Solid-state (13)C NMR spectroscopy was employed.
• Spectral patterns of alpha-indomethacin and gamma-indomethacin were analyzed.
• Temperature-dependent NMR studies were conducted on the alpha-form.

Main Results:

• Distinct chemical shift differences were observed between alpha- and gamma-indomethacin.
• Gamma-indomethacin exhibited single resonance signals for each carbon nucleus.
• Alpha-indomethacin showed complex, multi-signal resonances, indicating multiple conformations or disordered packing.
• Temperature variation (203-343 K) affected alpha-indomethacin signals without crystal transformation.

Conclusions:

• Solid-state (13)C NMR is a powerful technique for distinguishing indomethacin polymorphs.
• NMR spectral patterns provide insights into molecular conformation and packing within the crystal lattice.
• The study highlights the utility of NMR in characterizing solid-state forms and their conformational states.