Analysis of pharmaceuticals using near-infrared spectroscopy

Importance of the topic

Near-infrared spectroscopy has emerged as a rapid, nondestructive method for both qualitative and quantitative analysis in pharmaceutical development and manufacturing. It enables identification of raw materials, monitoring of blend uniformity, moisture analysis, coating thickness measurements, content verification and counterfeit detection without the use of reagents or lengthy sample preparation.

Objectives and overview

This bulletin presents an extensive collection of feasibility studies and practical applications of NIR spectroscopy in the pharmaceutical industry. It illustrates how NIR can be applied across a wide range of sample types—including powders, tablets, capsules, liquids, solutions and coated beads—to solve common analytical and process-control challenges.

Methodology and instrumentation

Most studies employed a spectral range from 1100 to 2500 nm using reflectance, transmission or interactance modes. Key instruments included:

• Model 5000 NIRSystems with reflectance, transmission and spinning-sample modules
• RapidContent Analyzer for solids and liquids
• RapidLiquid Analyzer with cuvette cells
• XDS MasterLab and SmartProbe analyzers with fiber-optic probes
• Model 6500 monochromator for transdermal patch analysis

Data evaluation ranged from simple univariate wavelength regressions to multivariate partial least squares models, with calibration errors (SEC) typically between 0.1 and 3 % depending on the analyte and sample matrix.

Main results and discussion

Applications demonstrated include:

• Identification of pharmaceutical raw materials (AMP, ADP, ATP, nucleic acids)
• Quantification of excipients such as lactose, starch, microcrystalline cellulose and stearic acid
• Monitoring moisture and fermentation parameters in powders, granulations, lyophilized products and broths
• Content uniformity and active ingredient quantification in cough syrups, analgesic tablets, antacids and transdermal patches
• Thickness measurements of film and ethyl cellulose coatings on tablets, beads and spheres
• Analysis of complex matrices such as toilet cleaners, antibacterial soaps and dietary powders

These studies confirm NIR sensitivity to chemical and physical attributes, enabling rapid screening and real-time monitoring throughout production.

Benefits and practical applications of the method

• Non-destructive testing without reagents
• Minimal or no sample preparation
• Fast analysis times (seconds per sample)
• Capability for in-line or at-line process monitoring
• Reduced operational costs and waste
• Support for quality by design and process analytical technology initiatives

Future trends and potential applications

Advances likely to enhance NIR usage include:

• Integration with fiber-optic probes for true in-line measurements
• Handheld and portable NIR instruments for field and laboratory flexibility
• Robust multivariate models leveraging machine learning to adapt across scales and formulations
• Expanded spectral libraries for rapid identification of new compounds and counterfeit detection
• Regulatory acceptance under PAT frameworks and Pharma 4.0 digitalization strategies

Conclusion

The broad range of applications covered in this bulletin underscores the versatility of near-infrared spectroscopy for pharmaceutical quality control and process monitoring. Its speed, ease of use and non-destructive nature make it an essential tool for modern analytical laboratories and manufacturing lines.

References

Application Bulletin AB-410, NIRSystems