Quantification of compaction-induced crystallinity reduction of a pharmaceutical solid using 19F solid-state NMR and...

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Science

Background:

• Quantifying the amorphous phase in pharmaceutical solids is critical for drug stability and bioavailability.
• Solid-state analytical techniques are essential for characterizing drug substance crystallinity.

Purpose of the Study:

• To investigate fluorine-19 solid-state nuclear magnetic resonance (NMR) as a quantitative analytical technique for amorphous content in a pharmaceutical candidate.
• To compare NMR-based quantification with established powder X-ray diffraction methods.

Main Methods:

• Utilized two (19)F T(1) relaxation-based NMR methods for crystallinity assessment.
• Employed both single and dual standard approaches for NMR quantification.
• Validated NMR results against powder X-ray diffraction (PXRD) data using linear calibration curves.

Main Results:

• (19)F solid-state NMR accurately quantified the amorphous phase in Compound 1.
• Excellent agreement was observed between NMR-derived crystallinity and PXRD calibration curve results.
• Both model-dependent and model-independent NMR methods yielded consistent quantification.

Conclusions:

• (19)F solid-state NMR is a powerful and reliable technique for determining amorphous content in pharmaceutical solids.
• NMR offers a valuable alternative or complementary method to PXRD for amorphous phase quantification.
• This technique is particularly useful for fluorine-containing pharmaceutical candidates.