Nondestructive, single tablet analysis using the NIRS XDS RapidContent Analyzer

Importance of the Topic

The analysis of solid dosage forms typically relies on HPLC, which is time-consuming and requires extensive sample preparation and solvents. Near-infrared spectroscopy (NIRS) offers a rapid, nondestructive alternative capable of reducing analysis time and eliminating solvent use, improving throughput and operational efficiency in pharmaceutical quality control.

Objectives and Study Overview

The main objective of this study was to demonstrate the feasibility of using the NIRS XDS RapidContent Analyzer for nondestructive, single-tablet analysis. Specific aims included:

• Assessing the ability of NIRS to quantify active ingredient content in 500 and 750 mg procainamide HCl tablets.
• Developing a robust calibration model based on second derivative spectra to minimize scattering effects.
• Validating the NIRS method against a reference HPLC assay.

Methodology

Reflectance spectra were collected for 100 individual tablets from each lot in the 1100–2500 nm range. Ten to twenty tablets showing spectral variation were further analyzed by HPLC. Second derivative transformation was applied to raw spectra to correct for multiplicative and surface scattering. Calibration models were built using regions with strong active ingredient absorption and correlated to HPLC results.

Used Instrumentation

• NIRS XDS RapidContent Analyzer equipped with a centering iris for sample positioning.
• Reflectance measurement mode in the 1100–2500 nm wavelength range.
• High-performance liquid chromatography (HPLC) system for reference analysis.

Key Results and Discussion

Second derivative preprocessing effectively removed scattering artifacts. For 750 mg tablets, the calibration at 1368 nm yielded a correlation coefficient of –0.84, a standard error of calibration (SEC) of 1.7 mg, and a maximum relative residual error of 0.53%. Validation on a second lot showed a standard error of prediction (SEP) of 1.4 mg and a maximum relative residual error of 0.43%. Analysis of 500 mg tablets produced similarly satisfactory results, demonstrating model robustness that improves as diversity in calibration samples increases.

Benefits and Practical Applications

NIRS enables assay results in under 30 seconds without sample preparation or solvents. Its nondestructive nature allows in situ application on production lines, eliminating the need for labeling, transport, and extensive separation steps. This method can be readily integrated into conventional QC labs or directly in manufacturing environments.

Future Trends and Potential Applications

As calibration datasets expand with more diverse tablet lots, predictive accuracy and robustness will further improve. Potential developments include:

• Extension to other dosage forms and active ingredients.
• Integration of real-time process analytical technology (PAT) for continuous monitoring.
• Advanced chemometric algorithms and machine learning approaches for enhanced specificity and sensitivity.

Conclusion

Near-infrared spectroscopy provides a fast, accurate, and nondestructive alternative to traditional HPLC assays for solid dosage forms. Its adoption can streamline quality control workflows, reduce operational costs, and support on-site testing in pharmaceutical production environments.