Direct comparison of low- and mid-frequency Raman spectroscopy for quantitative solid-state pharmaceutical analysis

Area of Science:

• Analytical Chemistry
• Materials Science
• Spectroscopy

Background:

• Quantitative analysis of solid-state mixtures is crucial in pharmaceutical development.
• Raman spectroscopy is a valuable tool for characterizing materials.
• Different solid-state forms of a drug can exhibit distinct spectral properties.

Purpose of the Study:

• To evaluate the potential of low-frequency (terahertz) Raman spectroscopy for quantitative analysis of ternary mixtures.
• To directly compare the performance of low-frequency and mid-frequency Raman spectral regions for mixture analysis.
• To present novel low-frequency Raman spectra for different piroxicam solid-state forms.

Main Methods:

• Utilized low-frequency and mid-frequency Raman spectroscopy.
• Analyzed ternary mixtures of piroxicam solid-state forms (β, α2, and monohydrate).
• Employed partial least squares regression (PLSR) for quantitative modeling.

Main Results:

• Both spectral regions yielded quantitative models for mixture prediction.
• Low-frequency Raman spectroscopy provided significantly lower prediction errors (RMSEP: 2.7-3.2%) compared to mid-frequency (RMSEP: 4.8-6.3%).
• Low-frequency spectra of piroxicam forms β, α2, and monohydrate were presented for the first time.

Conclusions:

• Low-frequency Raman spectroscopy demonstrates superior performance for quantitative analysis of solid-state mixtures.
• Enhanced spectral differences and signal-to-noise ratio in the low-frequency region contribute to improved model accuracy.
• This technique offers a promising approach for precise characterization of pharmaceutical crystalline forms.