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 solid dosage unit contains a consistent amount of active pharmaceutical ingredient (API). Traditional methods such as high-performance liquid chromatography (HPLC) are accurate but involve time-consuming sample preparation, solvent consumption, and potential sample destruction. Visible-near-infrared (Vis-NIR) spectroscopy offers a rapid, non-destructive alternative that can be implemented directly at production line stages, reducing analysis time and operational costs.

Objectives and study overview

This study aimed to develop and validate a Vis-NIR spectroscopic method for quantitative content uniformity testing of Cefixime tablets. By comparing Vis-NIR predictions against a reference HPLC method, the authors assessed accuracy, precision, and feasibility of implementing this technique for routine quality control.

Methodology

31 Cefixime tablet samples were analyzed without any sample preparation. Spectral data were collected in diffuse reflectance mode over a 400–2500 nm range using a NIRS XDS RapidContent Analyzer. Data preprocessing included second-derivative transformation and Standard Normal Variate (SNV) correction. Partial least squares (PLS) regression with four latent factors was applied. Calibration performance was evaluated via the coefficient of determination (R2), standard error of calibration (SEC), and standard error of cross-validation (SECV).

Used instrumentation

• NIRS XDS RapidContent Analyzer
• NIRS XDS iris sample positioning accessory
• Vision Air 2.0 Pharma Complete chemometric software

Main results and discussion

The final PLS model achieved an R2 of 0.968, indicating strong agreement between Vis-NIR predictions and HPLC reference values. The SEC was 1.6% and the SECV was 2.3%, with the latter comparable to the 1.5% standard error of the HPLC method. Selective wavelength ranges (1120–2300 nm and 2280–2346 nm) and preprocessing strategies effectively removed redundant spectral information and enhanced prediction robustness.

Benefits and practical applications

• Non-destructive analysis preserves samples for further testing.
• No chemical reagents or solvents are required, reducing costs and environmental impact.
• Rapid measurement enables at-line or in-line implementation within manufacturing processes.
• Minimal operator training is needed, lowering the risk of human error.

Future trends and applications

Advances in chemometric algorithms and instrumentation portability are driving wider adoption of Vis-NIR spectroscopy for pharmaceutical quality control. Emerging developments include fiber-optic probe integration for real-time monitoring, machine learning-driven model optimization, and expansion into liquid and semi-solid dosage forms. These trends support the principles of Process Analytical Technology (PAT) and continuous manufacturing.

Conclusion

This application note demonstrates that Vis-NIR spectroscopy with a RapidContent Analyzer provides a reliable, fast, and eco-friendly approach to content uniformity testing of Cefixime tablets. The achieved prediction errors are in line with traditional HPLC methods, confirming Vis-NIR as a viable alternative for routine quality assurance in pharmaceutical production.