Ultrafast magic angle spinning NMR characterization of pharmaceutical solid polymorphism: A posaconazole example

Area of Science:

• Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy
• Materials science
• Pharmaceutical analysis

Background:

• Protons are the most NMR-sensitive nuclei, crucial for pharmaceutical compound analysis.
• Low sensitivity in NMR often hinders the study of natural abundance drug substances.
• Proton-detected solid-state NMR under fast magic angle spinning (MAS) offers a solution to sensitivity challenges.

Purpose of the Study:

• To structurally characterize crystal polymorphs of the drug posaconazole.
• To demonstrate the utility of proton-detected solid-state NMR for analyzing pharmaceutical polymorphism.
• To investigate the distinct intermolecular packing in different posaconazole forms.

Main Methods:

• Utilized proton-detected solid-state NMR techniques.
• Employed fast magic angle spinning (MAS) at 100 kHz.
• Applied homo- and heteronuclear correlation spectroscopy.

Main Results:

• Achieved enhanced sensitivity and resolution for structural characterization.
• Successfully explored the distinct intermolecular packing in posaconazole forms I, III, and γ.
• Demonstrated the capability to analyze a large molecular weight drug (700.8 g·mol⁻¹) at natural abundance.

Conclusions:

• Proton-detected solid-state NMR is effective for detailed structural analysis of pharmaceutical polymorphism.
• Fast MAS NMR provides crucial insights into intermolecular packing differences between drug polymorphs.
• This methodology advances the characterization of drug substances and products at natural abundance.