Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System for Identifying and Detecting Salt Exchange in Pharmaceutical Tablets

Significance of the Topic

Maintaining the chemical form of active pharmaceutical ingredients (APIs) in solid dosage forms is essential to ensure consistent dissolution rates, stability, and bioavailability. Uncontrolled salt exchange, such as conversion between acid and salt forms under environmental stress, can compromise therapeutic efficacy and cause physical degradation of tablets.

Study Objectives and Overview

• Demonstrate the capability of the Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System to detect and map salt exchange in pharmaceutical tablets.
• Apply the technique to a case study of over-the-counter indigestion tablets that undergo citric acid to sodium citrate conversion under humidity exposure.
• Evaluate imaging speed, spatial resolution, and spectral identification performance for routine formulation development and troubleshooting.

Methodology

The LDIR system acquires molecular images by targeting a small number of diagnostically important mid-infrared wavelengths, enabling rapid whole-tablet scans. Imaging at any resolution is possible without optical adjustments, facilitating a two-step workflow: a fast overview scan followed by high-resolution mapping of regions showing salt formation. Individual pixel spectra in the fingerprint region can be matched against a reference library in seconds to classify chemical species.

Utilized Instrumentation

• Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System with automated ATR sampling option
• Integrated spectral library for APIs and excipients

Main Results and Discussion

Exposure of indigestion tablets to ambient humidity induced conversion of citric acid to sodium citrate in the presence of sodium bicarbonate, producing water and CO₂. LDIR images of a 7 × 7 mm tablet region acquired at 10 µm pixel size (11 min per scan) revealed the expanding sodium citrate domains around residual citric acid after 2 and 24 hours. Automated classification allowed rapid visualization of constituent distributions and quantification of salt formation kinetics.

Benefits and Practical Applications

• Rapid, non-destructive imaging of APIs and excipients without interference from fluorescence.
• Flexible spatial resolution for targeted analysis of critical regions.
• Automated operation reduces user training requirements and assay time, preserving sample integrity by minimizing humidity exposure.
• Walk-up usability supports formulation development, stability testing, and troubleshooting in R&D and QA/QC settings.
• Low maintenance with no requirement for liquid nitrogen cooling.

Future Trends and Opportunities

• Integration of advanced chemometric and machine-learning algorithms for enhanced classification and quantification.
• Real-time in-line or at-line monitoring of tablet production to detect formulation anomalies on the manufacturing floor.
• Miniaturization and automation improvements to accommodate higher throughput in pharmaceutical screening.
• Expansion of chemical imaging to other dosage forms such as capsules, pellets, and transdermal patches.

Conclusion

The Agilent 8700 LDIR Chemical Imaging System offers a fast, sensitive, and user-friendly approach for detecting and mapping salt exchange in pharmaceutical tablets. By combining rapid multi-scale imaging with automated spectral identification, it provides valuable insights into formulation stability and supports efficient development and quality control workflows.