Pharmaceutical Packaging Materials Quality Control and USP Chapter <661.1> Compliance

Significance of Topic

Adequate identification and quality control of pharmaceutical packaging materials are vital to ensure drug stability, prevent API degradation, and avoid costly product recalls. Mid-infrared FTIR spectroscopy offers a rapid chemical fingerprinting approach to confirm polymer compositions, detect impurities, and distinguish genuine packaging from counterfeits.

Objectives and Overview of Study

This study evaluates the performance of the Agilent Cary 630 FTIR with diamond ATR module for:

• Comparing polymer compositions of name-brand versus generic blister packs for over-the-counter medications
• Detecting counterfeit packaging by analyzing primary and secondary packaging materials
• Demonstrating compliance with USP General Chapter <661.1> requirements for plastic materials of construction

Methodology and Instrumentation

Samples of branded and generic cold-and-flu blister packs and their paper or polymer backings were purchased retail. FTIR spectra were collected on an Agilent Cary 630 FTIR spectrometer equipped with a diamond ATR accessory. Key measurement parameters:

• Spectral range: 4000–650 cm⁻¹
• Resolution: 4 cm⁻¹
• Scans co-added: 64
• Data analysis software: Agilent MicroLab FTIR with spectral library and automatic hit-quality index calculation

Both primary (blister layers and foil lidding) and secondary packaging (paper backings) were analyzed. Unknown spectra were compared to USP reference standards in a custom library and evaluated by hit-quality indexes.

Main Results and Discussion

• Generic blister packs predominantly used PVC/PVC bilayers, whereas name-brand products incorporated higher-performance polymers: PCTFE outer layers with PVC inner layers or PVC/PVDC combinations for reduced moisture vapor transmission rates.
• Presence of copolymers (styrene-butadiene rubber or polyacrylate) in PVC layers was quantified by characteristic absorbance bands (e.g., 1736 cm⁻¹ ester carbonyl) with hit-quality indexes >0.98.
• Unexpected layer configurations were identified in one generic pack (PVDC on the outer layer), highlighting potential quality issues or inadvertent material swaps.
• Analysis of paper backings revealed a genuine microcrystalline cellulose film for most products, while a counterfeit sample showed a styrene-acrylate copolymer with high mineral filler content.
• Library search results, supported by color-coded thresholds (green/yellow/red), provided clear pass/fail criteria for QA and counterfeit screening.

Benefits and Practical Applications

• Rapid qualification and identification of raw materials for pharmaceutical packaging in line with regulatory standards
• In-process quality assurance during packaging manufacture to prevent material inconsistencies
• Efficient detection of counterfeit products through polymer fingerprint comparison
• Quantitative measurement of copolymer additives to monitor formulation consistency
• Facilitation of USP <661.1> compliance by automated library matching and hit-quality reporting

Future Trends and Opportunities

Further developments may include expanded spectral libraries for emerging polymers, integration of IR-active marker compounds into packaging for secure authentication, inline or at-line FTIR monitoring in manufacturing, and coupling with AI-driven spectral interpretation to enhance sensitivity and throughput.

Conclusion

The Agilent Cary 630 FTIR with diamond ATR module and MicroLab software provides a robust, user-friendly platform for detailed polymer identification in pharmaceutical packaging. It enables precise differentiation between packaging materials used by various manufacturers, supports early detection of counterfeit or non-compliant products, and meets USP <661.1> requirements through automated spectral matching and quantifiable hit-quality indexes.

References

1. USP 43-NF 38 General Chapter <661.1>, Plastic Materials of Construction, 2025
2. USP 43-NF 38 General Chapter <1661>, Evaluation of Plastic Packaging Systems for Pharmaceutical Use, 2025
3. USP 34-NF 39 General Chapter <854>, Mid-Infrared Spectroscopy, 2011
4. USP 43-NF 38 General Chapter <197>, Spectrophotometric Identification Test, 2015
5. USP 43-NF 38 General Chapter <659>, Packaging and Storage Requirements, 2025
6. USP 43-NF 38 General Chapter <661>, Plastic Packaging and Materials of Construction, 2025
7. Pilchik R., Pharmaceutical Blister Packaging, Part I: Rationale and Materials, Pharmaceutical Technology, 2000, 24(11):68–78
8. Service Industries and Sepha Ltd, Considerations for Selecting Blister Packaging Materials for Pharmaceutical Products, Pharmaceutical Online, 2012