Terahertz spectroscopy to identify the polymorphs in freeze-dried Mannitol

Area of Science:

• Solid-state characterization
• Pharmaceutical sciences
• Terahertz spectroscopy

Background:

• Mannitol is a crucial excipient in pharmaceutical freeze-drying processes.
• Polymorphism of Mannitol significantly impacts its physical properties and drug product performance.
• Accurate identification of Mannitol polymorphs is essential for quality control.

Purpose of the Study:

• To demonstrate the application of terahertz time-domain spectroscopy (THz-TDS) for identifying Mannitol polymorphs.
• To investigate the influence of various freeze-drying techniques on Mannitol polymorph formation.
• To correlate THz-TDS findings with established X-ray diffraction methods.

Main Methods:

• Terahertz time-domain spectroscopy (THz-TDS) was employed in the 0.1–7.5 THz frequency range.
• Different freeze-drying techniques were applied to Mannitol samples.
• Polymorph identification was confirmed using conventional X-ray diffraction.

Main Results:

• THz-TDS successfully differentiated between Mannitol polymorphs.
• Freeze-drying techniques resulted in either the delta form or a mixture of delta and beta forms of Mannitol.
• Results from THz-TDS were consistent with X-ray diffraction measurements.

Conclusions:

• Terahertz time-domain spectroscopy is a viable technique for rapid and non-destructive identification of Mannitol polymorphs.
• The choice of freeze-drying method directly influences the resulting Mannitol crystalline form.
• This study validates THz-TDS as a complementary tool for pharmaceutical solid-state analysis.