Analysis of pharmaceuticals using near-infrared spectroscopy

Importance of the Topic

Near-infrared (NIR) spectroscopy provides rapid, non-destructive analysis for pharmaceutical materials and processes. Its applications span raw-material identification, blend uniformity, moisture and active-ingredient quantification, coating thickness measurement, counterfeit detection, and in-situ moisture monitoring in sealed containers or lyophilized products. Adoption in pharmacopeial monographs and regulatory frameworks underscores its value in quality assurance and process analytical technology.

Goals and Study Overview

This bulletin illustrates 47 application studies using NIR spectroscopy to:

• Qualitatively identify raw materials, actives, placebos, and mixtures.
• Quantitatively monitor active ingredients, excipients, moisture, and coating thickness.
• Assess feasibility of in-situ and non-contact measurements through vials, bags, tablets, capsules, fermentation broths, and adhesive patches.
• Demonstrate spectral regions and data-analysis approaches suited to each analyte and matrix.

Methodology and Instrumentation

Across these studies, NIR measurements were typically conducted over 1100–2500 nm using reflectance or transmission sampling modes. Common instrumentation included:

• NIRS XDS family (RapidContent, RapidLiquid, SmartProbe, MasterLab) equipped with reflectance and transmission modules.
• Model 6500 monochromator with fiber-optic or transflectance probes.
• Sample handling accessories: spinning and horizontal sample modules, powder cells, cuvettes (0.5–2 mm pathlength), and sealed vial mounts.

Data analysis employed univariate wavelength regressions at distinctive absorption peaks (e.g., 1440, 1680, 1940, 2250 nm) or multivariate Partial Least Squares (PLS) models to resolve overlapping bands or complex matrices.

Key Results and Discussion

Qualitative identification success was reported for nucleic acids, amino acids, proteins, tablets, capsules, placebos, and beverage concentrates based on unique spectral signatures and library matching. Quantitative models achieved standard errors of calibration (SECs) in the ranges:

• Actives in tablets or syrups: 0.01–0.4% w/w.
• Coating thickness: 0.07–0.2% (w/w) or 0.02 mg/cm² in patches.
• Excipient levels (calcium carbonate, lactose, starch): 0.6–2.9% w/w.
• Moisture in powders and lyophilized solids: 0.1–0.3% w/w.
• Fermentation metabolites: 0.04–0.06 mg/mL.

In-situ measurements directly through glass vials or plastic bags proved feasible, enabling real-time monitoring without sample removal. Critical factors influencing precision included particle size, sample homogeneity, container wall thickness, and scattering effects corrected via divisor terms or dual-wavelength approaches.

Method Benefits and Practical Applications

NIR spectroscopy delivers fast, solvent-free, and operator-safe analysis adaptable to in-line, at-line, or off-line process monitoring. It minimizes sample preparation, supports PAT initiatives, and enhances throughput in QA/QC laboratories. Specific benefits include:

• Immediate raw-material verification to prevent mix-ups.
• Blend uniformity checks to ensure content consistency.
• Real-time moisture and drying endpoints to optimize granulation and lyophilization cycles.
• Coating thickness control for targeted release profiles.
• Counterfeit detection via spectral fingerprinting.

Future Trends and Opportunities

Advances in portable and handheld NIR spectrometers will broaden field applications, enabling on-site counterfeit screening and supply-chain verification. Integration with machine learning and internet-of-things (IoT) networks promises self-optimizing processes and digital-twins for continuous manufacturing. Emerging hyperspectral imaging approaches may extend spatial resolution in tablet or coating uniformity studies. Finally, expanding regulatory acceptance will drive broader deployment in sterility assurance, biologics monitoring, and single-use systems.

Conclusion

Near-infrared spectroscopy has proven its versatility in pharmaceutical analysis through diverse examples of qualitative and quantitative studies. Its non-destructive, rapid, and reagent-free nature makes it an ideal tool for ensuring raw material identity, blend uniformity, moisture levels, active content, and process consistency. Ongoing instrument miniaturization, advanced chemometrics, and regulatory support will further strengthen its role in quality control and process analytical technology.