Dynamic nuclear polarization enhanced NMR spectroscopy for pharmaceutical formulations

Area of Science:

• Solid-state NMR spectroscopy
• Pharmaceutical analysis
• Materials characterization

Background:

• Characterizing pharmaceutical formulations at the atomic level is crucial for quality control.
• Traditional NMR methods may require sample modification or lack sensitivity for complex formulations.
• Dynamic Nuclear Polarization (DNP) offers enhanced sensitivity for solid-state NMR.

Purpose of the Study:

• To demonstrate the utility of DNP-enhanced solid-state NMR for characterizing commercial pharmaceutical formulations.
• To analyze the atomic-level structure and interactions within drug products.
• To determine the physical form and particle size of active pharmaceutical ingredients (APIs).

Main Methods:

• Utilized DNP-enhanced solid-state NMR spectroscopy at 9.4 T.
• Impregnated gently ground tablets with biradical polarizing agents in 1,1,2,2-tetrachloroethane.
• Acquired one- and two-dimensional 13C and 15N solid-state NMR spectra at 105 K.
• Analyzed DNP enhancements (ε) as a function of polarization time to model nuclear spin diffusion.

Main Results:

• Achieved DNP enhancements (ε) of 40-90 for cetirizine dihydrochloride in four commercial formulations.
• Successfully identified the amorphous form of the API within the tablets.
• Observed direct API-povidone interactions using 1H-15N correlation spectra.
• Determined API domain sizes, with particle radii around 0.07 μm using Weibull distribution modeling.

Conclusions:

• DNP-enhanced solid-state NMR is a powerful, non-destructive technique for detailed characterization of pharmaceutical formulations.
• The method allows for rapid acquisition of high-quality spectra, preserving microstructural information.
• It provides insights into API physical form, particle size, and drug-excipient interactions.