Discriminating the Interaction Anisotropy in Polymorphs Using Powder Brillouin Light Scattering

Area of Science:

• Materials Science
• Solid-State Chemistry
• Analytical Chemistry

Background:

• Drug product performance is critically dependent on solid-state form (polymorphism).
• Current methods like Powder X-ray Diffraction (PXRD) are effective but not always suitable for continuous manufacturing.
• There is a need for advanced Process Analytical Technologies (PATs) for real-time, non-destructive polymorph monitoring.

Purpose of the Study:

• To introduce and validate powder Brillouin light scattering (p-BLS) as a novel PAT for discriminating between polymorphic forms of molecular solids.
• To investigate the relationship between intermolecular forces and acoustic properties measurable by p-BLS.
• To demonstrate the potential of p-BLS for in situ monitoring of solid-state transformations in pharmaceutical manufacturing.

Main Methods:

• Application of powder Brillouin light scattering (p-BLS) to three model compounds (resorcinol, sulfamerazine, furosemide).
• Analysis of anisotropic sound velocities and acoustic frequency distributions obtained from p-BLS spectra.
• Interpretation of p-BLS data using hydrogen-bond analysis and computational energy frameworks (CrystalExplorer).

Main Results:

• Distinct, polymorph-specific acoustic frequency distributions were successfully obtained using p-BLS.
• The observed sound frequencies directly correlated with the strength and orientation of intermolecular forces within the crystal structures.
• p-BLS demonstrated a reliable capability for discriminating between different polymorphic forms.

Conclusions:

• p-BLS is a novel optical technique sensitive to intermolecular interaction forces in molecular solids.
• p-BLS can reliably discriminate between polymorphs, offering a valuable alternative to traditional methods.
• The technique holds significant potential for monitoring various pharmaceutically relevant processes like hydrate formation and co-crystallization in real-time.