Rapid Discrimination and Classification of Polymorphs Using the Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System

Significance of the Topic

Characterizing pharmaceutical polymorphs is critical because different crystal forms of an active ingredient can exhibit vastly different solubility, stability, bioavailability and therapeutic performance. Reliable polymorph analysis supports consistent product quality and efficacy throughout drug development and manufacturing.

Objectives and Study Overview

This application demonstrates the use of the Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System to rapidly discriminate and classify carbamazepine polymorphs in solid dosage forms. Focus is placed on distinguishing the therapeutically active form III from the non-therapeutic form I, mapping their spatial distribution and quantifying relative amounts alongside a cellulose excipient.

Methodology and Instrumentation

The method begins by collecting reference reflectance spectra for carbamazepine forms I and III and the cellulose excipient. Agilent Clarity software then selects key diagnostic wavelengths for each component, enabling a rapid imaging protocol. Tablets (13 mm diameter) were imaged in reflectance mode at 10 μm pixel resolution.

• Instrumentation Used
  • Agilent 8700 LDIR Chemical Imaging System
  • Agilent Clarity Software for spectral selection and classification

Key Results and Discussion

Complete classification imaging of a 13 mm tablet required only 27 minutes at 10 μm resolution. Two formulations were analyzed: one containing 5.2 % form I, 15.4 % form III; the other 15.3 % form I, 5.5 % form III (rest cellulose). The measured surface concentrations matched known weight percentages, confirming accurate spatial mapping and relative quantification. High-resolution ATR imaging (down to 0.1 μm) further enables detailed crystal growth studies.

Benefits and Practical Applications

• Rapid discrimination and mapping of polymorphs without lengthy spectral scans
• High spatial resolution imaging supports both full-tablet scans and localized studies
• Relative quantification of APIs and excipients without separate calibration curves
• Real-time monitoring of polymorph conversion during formulation development

Future Trends and Opportunities

Advancements may include integration of LDIR imaging with in-line process monitoring for continuous manufacturing, application to a broader range of APIs and excipients, development of advanced chemometric and AI-driven image analysis for automated classification, and expansion of megapixel ATR mapping for nanoscale polymorph behavior studies.

Conclusion

The Agilent 8700 LDIR system offers a fast, high-resolution approach for discriminating pharmaceutical polymorphs in solid dosage forms. Its ability to image entire tablets and quantify relative component distributions makes it a valuable tool for formulation development, quality control and ensuring therapeutic consistency.

Reference

1. Czernicki W, Baranska M. Carbamazepine polymorphs: Theoretical and experimental vibrational spectroscopy studies. Vibrational Spectroscopy. 2013;65:12–23.
2. Grzesiak AL, Lang M, Kim K, Matzger AJ. Comparison of the four anhydrous polymorphs of carbamazepine and the crystal structure of form I. J Pharm Sci. 2003;92:2260–2271.