Terahertz Spectroscopic Imaging of Polymorphic Forms in Pharmaceutical Crystals

Abstract

A terahertz spectroscopic imaging system was fabricated for the detection of two-dimensional molecular distributions in pharmaceutical tablets based on absorption peaks of intermolecular or intramolecular hydrogen bonds in crystals. The terahertz imaging system consists of a terahertz time-domain spectrometer and a three-dimension translational stage. Using the system, we obtained frequency-dependent terahertz images of famotidine polymorphic forms A and B. An offset subtraction process is useful for detecting the distribution in an inhomogeneous tablet containing a mixture of the two forms. The terahertz imaging technique is a valuable tool for the analysis of polymorphic forms of crystal in inhomogeneous pharmaceutical tablets.

Keywords:

• Famotidine
• hydrogen bonding
• pharmaceutical tablets
• polymorphism
• terahertz imaging

Acknowledgment

We thank Miho Kanazawa (NTT-AT) for helping to purify the famotidine, and Ms. Rahel Park and Ms. Aya Kashifuku for assistance in the DSC measurement.