Microanalysis in Pharmaceutical Product Development and Trouble-Shooting

Importance of the Topic

Pharmaceutical products require stringent quality control to ensure correct composition and absence of contaminants. While bulk methods like mid- and near-IR spectroscopy verify overall identity, they lack spatial resolution. Microscopic FTIR addresses this gap by identifying microscopic particles, inclusions and mapping component distributions, critical for troubleshooting and formulation development.

Objectives and Study Overview

This application note illustrates how the LUMOS II FTIR microscope, combined with ATR and mapping capabilities and comprehensive spectral libraries, can:

• Identify and characterize contamination particles and tablet inclusions.
• Determine the chemical identity of particles in sterile formulations.
• Map the spatial distribution of active pharmaceutical ingredients (API) and excipients in tablets.

Used Instrumentation

• LUMOS II FTIR microscope (compact, fully automated)
• OPUS spectroscopic software with OPUS/SEARCH and OPUS/3D modules
• ATR-COMPLETE spectral library (over 26 000 spectra)

Methodology

Measurement procedures employed include:

• ATR mode for direct sampling without preparation, using a micro-vice to secure tablets or filter substrates.
• Microscale mapping with spatial resolution down to 10×10 µm for spot measurements and 25×25 µm for mapping across areas up to 500×325 µm.
• Isolation of particles from liquid formulations onto gold filters for direct ATR analysis.
• Automated data acquisition (approx. 10 s per spectrum) and library searches for rapid identification.
• Linear combination analysis of pure-component spectra to generate chemical distribution images.

Main Results and Discussion

• Tablet Inclusion Analysis: A yellow inclusion inside a tablet was quickly identified as magnesium stearate, clearly distinct from the surrounding matrix.
• Particle Identification in Liquids: Fibers filtered from a biopharmaceutical formulation showed characteristic PTFE (Teflon) peaks, indicating filter or stopper abrasion rather than formulation precipitate.
• API and Excipients Mapping: ATR mapping of an ibuprofen tablet visualized the spatial distributions of API and excipients (lactose, microcrystalline cellulose, sodium dodecyl sulfate) through false-color chemical images.

Benefits and Practical Applications

• Rapid, precise identification of microscopic contaminants to trace sources of quality issues.
• Insight into formulation homogeneity to support product optimization and controlled release.
• User-friendly, fully automated instrumentation suitable for routine QC and research laboratories.

Future Trends and Possibilities

Advances may include higher spatial resolution for nanoscale analysis, expanded spectral libraries for novel materials, integration with machine learning for automated spectral interpretation, and multi-modal imaging combining FTIR with Raman or other techniques for comprehensive characterization.

Conclusion

Micro-FTIR using the LUMOS II microscope offers a robust, user-friendly approach for detecting and characterizing microscopic contaminants, mapping component distributions, and supporting pharmaceutical development and troubleshooting. Its automation and intuitive software enable efficient, reproducible analyses essential for modern quality control and formulation science.