Quantitative evaluation of mefenamic acid polymorphs by terahertz-chemometrics

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Spectroscopy

Background:

• Polymorphism significantly impacts drug efficacy and stability.
• Accurate quantification of polymorphic content is crucial for pharmaceutical quality control.
• Traditional methods for polymorph analysis can be time-consuming and destructive.

Purpose of the Study:

• To develop and validate a quantitative method for mefenamic acid polymorphs using terahertz (THz) spectroscopy.
• To assess the utility of THz-spectroscopy combined with chemometrics for polymorph analysis.
• To establish a rapid and non-destructive technique for pharmaceutical analysis.

Main Methods:

• Preparation of mefenamic acid polymorphic forms I and II via recrystallization.
• Creation of eleven standard samples with varying polymorphic form I content (0-100%) through physical mixing.
• Acquisition of THz spectra using a frequency-tunable THz spectrometer.
• Data analysis using partial least square regression after spectral smoothing, normalization, and pretreatment.
• Investigation of spectral data management effects on chemometric model parameters.

Main Results:

• THz spectra of all standard samples exhibited an isosbestic point at 3.70 THz.
• The best linear correlation was observed between predicted and actual form I content.
• Key spectral features at 1.45 THz (highest) and 2.25 THz (lowest) were identified in the regression vector.
• Chemometric models demonstrated the effectiveness of THz-spectroscopy for quantitative polymorph analysis.

Conclusions:

• THz-spectroscopy, coupled with chemometrics, provides a valuable tool for quantitative analysis of mefenamic acid polymorphs.
• The developed method is rapid, non-destructive, and suitable for pharmaceutical industry applications.
• This technique facilitates efficient quality control and characterization of drug substances.