Structural analysis of polymorphism and solvation in tranilast

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Tranilast exhibits polymorphism, impacting its solid-state properties.
• Understanding different polymorphic forms is vital for drug development and formulation.

Purpose of the Study:

• To characterize five distinct polymorphic forms of tranilast.
• To elucidate structural and spectral differences between anhydrous forms and solvates.
• To assess the suitability of spectroscopic methods for distinguishing tranilast polymorphs.

Main Methods:

• Single-crystal X-ray diffraction (SCXRD) for crystal structure determination.
• Solid-state nuclear magnetic resonance (ssNMR) spectroscopy.
• Fourier transform infrared (FTIR) and Fourier transform-Raman (FT-Raman) spectroscopy.
• Thermal analysis (e.g., DSC, TGA).

Main Results:

• Crystal structures of the most stable anhydrous form (Form I), a chloroform solvate, and a dichloromethane solvate were determined.
• Two additional anhydrous forms (Form II and Form III) were studied but not amenable to SCXRD.
• Spectroscopic analysis revealed distinct patterns for each form, with Form II showing unique characteristics possibly due to conformational changes and hydrogen bonding.
• Form III was identified as a packing and hydrogen-bonding polymorph with altered intermolecular interactions.

Conclusions:

• Spectroscopic techniques, particularly ssNMR and vibrational spectroscopy, can reliably differentiate between anhydrous tranilast polymorphs.
• Despite similar thermal behaviors, spectroscopic methods are essential for quality control in pharmaceutical development of tranilast.
• Polymorphism in tranilast significantly influences molecular conformation, hydrogen bonding, and crystal packing.