Terahertz frequency-domain sensing combined with quantitative multivariate analysis for pharmaceutical tablet...

Area of Science:

• Pharmaceutical analysis
• Spectroscopy
• Chemometrics

Background:

• Near-infrared (NIR) and Raman spectroscopy are standard for pharmaceutical analysis but sensitive to particle size and poor for physical properties like density.
• Terahertz (THz) frequency-domain spectroscopy offers low scattering, making it suitable for characterizing both chemical and physical properties of pharmaceutical tablets.

Purpose of the Study:

• To explore the feasibility of THz spectroscopy combined with multivariate analysis for quantifying active pharmaceutical ingredient (API) concentration and tablet density.
• To compare the performance of THz spectroscopy against established techniques like NIR and Raman for pharmaceutical tablet characterization.

Main Methods:

• 33 pharmaceutical tablets with varying Ibuprofen (API) concentration and filler particle size were analyzed using THz frequency-domain spectroscopy (750 GHz–1.5 THz).
• Orthogonal Partial Least Squares (OPLS) regression was applied to pre-processed spectral data to develop quantitative prediction models.
• Model performance was evaluated using coefficient of determination (R²) and relative prediction errors on test sets.

Main Results:

• A high-quality model was developed for tablet density (R² = 0.97, relative error = 0.7%).
• A fair model was achieved for API concentration (R² = 0.98, relative error = 6%).
• THz spectroscopy demonstrated low scattering effects, advantageous for tablet analysis.

Conclusions:

• Terahertz spectroscopy is a valuable complementary technique to NIR and Raman spectroscopy for pharmaceutical tablet analysis.
• It enables accurate characterization of physical properties, such as tablet density, and quantification of API concentration with reduced scattering interference.