Content uniformity of pharmaceutical solid dosage forms using Vis-NIR spectroscopy

Importance of the Topic

The uniformity of active pharmaceutical ingredients in solid dosage forms is a critical quality parameter in pharmaceutical manufacturing. Traditional methods based on high-performance liquid chromatography require extensive sample preparation and solvent consumption, leading to significant time and cost burdens. Vis–NIR spectroscopy offers a non-destructive, rapid alternative that can analyze tablets directly, reducing analysis time from hours to minutes and eliminating the need for solvents.

Objectives and Study Overview

This study aims to demonstrate the capability of Metrohm Vis–NIR analyzers to assess content uniformity in pharmaceutical tablets. Ceftazidime tablets were selected as model samples to develop quantitative methods for the API and key excipients. The study evaluated method performance by comparing Vis–NIR predictions with established reference assay results.

Methodology and Instrumentation

A total of 38 tablet samples were provided, with five used for external validation and 33 for calibration. Reflectance spectra were collected over the 400 to 2500 nm range using:

• NIRS XDS RapidContent Analyzer – Metrohm 2.921.1110
• NIRS XDS iris sample holder – Metrohm 6.7425.000
• Vision Air 2.0 Pharma Complete software – Metrohm 6.6072.209

Data processing involved partial least squares regression with second derivative spectral pre-treatment and selection of analyte-specific wavelength intervals to optimize predictive performance.

Key Results and Discussion

Vis–NIR methods achieved high correlation with reference assays for the active ingredient and excipients:

• API content (ceftazidime): R² 0.984, SEC 1.5%, SECV 1.9%, SEP 2.1%
• Starch excipient: R² 0.944, SEC 1.0%, SECV 1.1%, SEP 1.7%
• Sodium carbonate excipient: R² 0.966, SEC 1.7%, SECV 1.8%, SEP 2.4%

The errors of prediction were comparable to the reference HPLC method, demonstrating the robustness of Vis–NIR as an alternative analytical tool.

Benefits and Practical Applications

Vis–NIR spectroscopy enables:

• Non-destructive analysis of tablets without sample preparation
• Rapid measurement with results in under one minute per unit
• Significant reduction in solvent use and associated costs
• Potential for both offline and online quality control implementations

Future Trends and Opportunities

Further developments may include:

• Extension of Vis–NIR methods to other solid and liquid dosage forms
• Integration with process analytical technology frameworks for real-time monitoring
• Advanced spectral algorithms and machine learning for improved sensitivity
• Miniaturization and portable NIR devices for in-field testing

Conclusion

Metrohm Vis–NIR spectroscopy demonstrates reliable performance for assessing content uniformity in pharmaceutical tablets. The technique offers fast, cost-effective, and environmentally friendly analysis, with performance metrics comparable to traditional methods. Adoption of Vis–NIR can enhance quality control workflows and support continuous manufacturing strategies.

References

• Metrohm 2018 NIR Application Note NIR-063 Content Uniformity of Pharmaceutical Solid Dosage Forms using Vis–NIR Spectroscopy Version 1