Identification Test of the Ibuprofen Active Ingredient Compliant with European Pharmacopoeia and United States Pharmacopeia and Analysis of Final Product (Commercial Pharmaceutical) by ATR Method

Importance of the Topic

Infrared spectroscopy is a crucial analytical tool in pharmaceutical quality control, offering rapid identification of active pharmaceutical ingredients (APIs) and finished products in compliance with global pharmacopeial standards. This capability supports drug safety and regulatory adherence under diverse environmental conditions.

Study Objectives and Overview

This study evaluates the identification testing of ibuprofen, a nonsteroidal anti-inflammatory drug, using Fourier transform infrared (FTIR) spectroscopy. It compares methods prescribed by the European Pharmacopoeia (EP), United States Pharmacopeia (USP-NF), and explores analysis of finished drug formulations.

Methodology and Instrumentation

• Instrument: Shimadzu IRSpirit-ZX FTIR spectrophotometer
• ATR Attachment: QATR-S single-reflection diamond crystal
• KBr Pellet Preparation: Pixie mini hydraulic press forming 7 mm pellets
• Measurement Conditions:
  • Wavenumber range: 4 000–550 cm⁻¹ (EP) / 3 800–650 cm⁻¹ (USP-NF)
  • Resolution: 2 cm⁻¹, 45 scans, SqrTriangle apodization, DLATGS detector
• Identification Techniques: KBr pellet, ATR, and paste (Nujol) methods

Main Results and Discussion

• EP-Compliant KBr Pellet vs ATR:
  • Spectra from test samples closely matched the ibuprofen CRS reference.
  • ATR spectra showed slight peak shifts at high-absorption bands due to refractive index effects.
• USP-NF Paste Method:
  • Test and reference spectra overlapped after mixing with liquid paraffin; characteristic peaks of ibuprofen remained identifiable despite oil absorption regions.
• Final Product Analysis:
  • Direct ATR measurement of tablet coating revealed cellulose and talc via library search.
  • ATR on ground tablet powder, followed by spectral subtraction, identified additional excipients such as caffeine and silicate.

Benefits and Practical Applications

• Compliance: Meets EP and USP-NF requirements for API identification.
• Versatility: Multiple sampling techniques allow analysis of raw materials and finished formulations.
• Efficiency: ATR requires minimal sample preparation and supports surface-specific analysis.
• Robustness: The ZX model tolerates high temperature and humidity environments.
• Software Integration: LabSolutions IR with IR Pilot automates workflows and provides spectral advice for standardized testing.

Future Trends and Potential Applications

• Expansion of ATR imaging for spatially resolved analysis of multicomponent tablets.
• Integration with hyphenated techniques (e.g., FTIR-MS) for simultaneous identification and structural elucidation.
• Development of portable or handheld FTIR devices for on-site quality control.
• Implementation of advanced chemometric and AI algorithms for automated spectral interpretation and real-time monitoring.

Conclusion

Consistent use of sampling techniques is essential for reliable identification of ibuprofen and other pharmaceuticals. The IRSpirit-ZX system, equipped with ATR and pellet analysis capabilities, offers a compact, humidity-resistant solution that addresses pharmacopeial requirements and streamlines both API and finished product testing.

Instrumentation Used

• Shimadzu IRSpirit-ZX FTIR spectrophotometer
• QATR-S single-reflection ATR (diamond crystal) attachment
• Pixie mini hydraulic pellet press
• LabSolutions IR software with IR Pilot module

References

1. European Pharmacopoeia Supplement 11.2 (2023).
2. The United States Pharmacopeia-National Formulary 2023 Issue 2.
3. Rastogi A. et al., J. Environ. Manag. 2021, 300, 113694.
4. FTIR Talk Letter Vol. 1.
5. FTIR Talk Letter Vol. 2.
6. FTIR Talk Letter Vol. 38.