# New Findings on the Crystal Polymorphism of Imepitoin

## TL;DR

Researchers discovered a new stable form of the anticonvulsant drug imepitoin, which could impact its production and use in veterinary medicine.

## Contribution

A new metastable polymorph of imepitoin (polymorph II) was identified and fully characterized.

## Key findings

- Polymorph II of imepitoin was found to be metastable under ambient conditions for at least one year.
- The crystal structure of polymorph II was determined using synchrotron X-ray powder diffraction.
- Polymorph II forms a monotropic relationship with the known polymorph I.

## Abstract

Scientific and industrial reasons dictate the study of the solid state of imepitoin, a highly safe and tolerable anticonvulsant drug used in the therapy of epileptic dogs that was approved in the Europe Union in 2013. Our investigations allowed us to discover the existence of a new polymorph of imepitoin, which finds itself in a monotropic relationship with the crystalline form (polymorph I) already known and present on the market. This form (polymorph II), obtained by crystallization from xylene, remains metastable under ambient conditions for at least 1 year. Both solid forms were characterized by thermal (DSC and TGA), spectroscopic (FT-IR and Raman), microscopic (SEM and HSM), and diffractometric techniques. The thermodynamic relationship between the two polymorphs (monotropic) is such that it is not possible to study the melting of polymorph II, not even by adopting appropriate experimental strategies. Our measurements highlighted that the melting peak of imepitoin actually also includes an onset of melt decomposition. The ab initio structure solution, obtained from synchrotron X-ray powder diffraction data collected at room temperature, allowed us to determine the crystal structure of the new polymorph (II). It crystallizes in the monoclinic crystal structure, P21/c space group (#14), with a = 14.8687(6) Å, b = 7.2434(2) Å, c = 12.5592(4) Å, β = 107.5586(8)°, V = 1289.61(8) Å3, and Z = 4.