Chemical Imaging of Tablet Surfaces

Significance of the Topic

The spatial mapping of active pharmaceutical ingredients and excipients on tablet surfaces is critical for understanding formulation performance, stability, and therapeutic efficacy.

Study Objectives and Overview

This work demonstrates the application of the Agilent 8700 Laser Direct Infrared (LDIR) chemical imaging system to generate complete chemical maps of solid dosage forms within hours, addressing the time and expertise limitations of conventional Raman, FTIR, and NIR imaging techniques.

Methodology and Instrumentation Used

The 8700 LDIR system employs a Quantum Cascade Laser (QCL) to illuminate the sample and capture mid-infrared reflectance data across the tablet surface.

• Sample mounting: multiple tablets on microscope slides
• Resolution: 10 µm pixel size (down to 1 µm for high-resolution areas)
• Field of view: adjustable to cover entire tablet (e.g., 11 mm diameter)
• Detection: room-temperature detector without need for cryogenic cooling
• Software: automated image acquisition and spectral analysis

Main Results and Discussion

Using a model headache tablet containing acetaminophen, aspirin, caffeine, and four excipients, the system produced a high-resolution chemical map over an 11 mm tablet diameter in one hour. Key observations include:

• Clear spatial distribution of APIs and excipients with color-coded identification
• Visualization of cluster size, shape, and mixing homogeneity
• Detection of polymorphic forms and potential degradation products over time

The LDIR approach outperforms traditional methods by eliminating fluorescence interference, reducing acquisition time from days to hours, and requiring minimal operator expertise.

Benefits and Practical Applications of the Method

The rapid, high-resolution imaging enables:

• Accelerated formulation development and troubleshooting in production environments
• Efficient quality control of tablet homogeneity and component distribution
• Time-resolved stability studies to monitor API degradation pathways
• Correlation of physicochemical maps with dissolution behavior and therapeutic performance

Future Trends and Potential Applications

Advancements may include:

• Integration of LDIR imaging into in-line manufacturing for real-time process monitoring
• Enhanced software algorithms for automated defect detection and predictive analytics
• Extension of the technique to diverse dosage forms such as coatings and multilayer tablets
• Development of multimodal imaging combining LDIR with Raman or fluorescence modalities

Conclusion

The Agilent 8700 LDIR system represents a significant step forward in chemical imaging of tablet surfaces, offering speed, high spatial resolution, and ease-of-use. Its adoption can streamline formulation workflows, improve quality assurance, and support regulatory compliance in pharmaceutical development.

References

Agilent Technologies, Inc. (2021) Chemical Imaging of Tablet Surfaces Using the Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System. DE44332.8006018518, 5991-7513EN, May 17, 2021.