Content uniformity of pharmaceutical solid dosage forms using Vis-NIR spectroscopy exemplified on Cefixime tablets

Importance of the Topic

Content uniformity is a critical quality attribute in pharmaceutical manufacturing, ensuring that each dosage unit contains the intended amount of active ingredient. Reliable and efficient testing methods help maintain product safety, regulatory compliance, and patient efficacy.

Objectives and Study Overview

This application note demonstrates the feasibility of using visible–near-infrared (Vis-NIR) spectroscopy to assess the content uniformity of Cefixime tablets. The study compares Vis-NIR predictions against a reference HPLC method to evaluate analytical performance and operational advantages.

Methodology

• Sample set: 31 Cefixime tablet units from a single production batch.
• Spectral acquisition: Reflection mode covering 400–2500 nm on a NIRS XDS RapidContent Analyzer.
• Sample positioning: Automated iris accessory to ensure reproducible measurements.
• Data processing: Spectral pre-treatments including second derivative and Standard Normal Variate normalization.
• Wavelength selection: Primary range 1120–2300 nm; additional focus 2280–2346 nm for analyte-specific features.
• Calibration: Partial least squares (PLS) regression with four latent factors.
• Reference method error: HPLC standard error estimated at 1.5 %.

Used Instrumentation

• NIRS XDS RapidContent Analyzer (Metrohm 2.921.1110).
• NIRS XDS iris sample adapter (Metrohm 6.7425.000).
• Vision Air 2.0 Pharma Complete software (Metrohm 6.6072.209).

Key Results and Discussion

The PLS model yielded a correlation coefficient (R²) of 0.968, indicating strong agreement between Vis-NIR predictions and HPLC measurements. The standard error of calibration (SEC) was 1.6 %, while cross-validation error (SECV) reached 2.3 %, closely matching the reference method’s precision. These results confirm that Vis-NIR spectroscopy can reliably quantify Cefixime content without sample destruction or extensive preparation.

Benefits and Practical Applications

• Rapid, non-destructive testing enabling in-line or at-line quality control.
• Elimination of solvent use and reduction of laboratory waste.
• Minimized operator training and handling errors.
• Potential for real-time monitoring across production stages.

Future Trends and Potential Applications

• Integration of Vis-NIR sensors into continuous manufacturing and process analytical technology (PAT) frameworks.
• Application of advanced chemometric and machine-learning algorithms for enhanced predictive accuracy.
• Expansion of methodology to liquid and semi-solid dosage forms.
• Deployment in broader spectral ranges and miniature portable analyzers for field testing.

Conclusion

The Vis-NIR method developed for Cefixime tablets provides comparable accuracy to HPLC with significant time and resource savings. Its non-destructive nature and operational simplicity make it an attractive alternative for routine content uniformity testing in pharmaceutical quality control.

References

• Metrohm Application Note NIR-066, Version 1, September 2018