Thermal expansion behaviors of the new antiepileptic drug brivaracetam

The purpose of the study was to investigate the thermal expansion characteristics of brivaracetam form I, and explore the influence mechanism of the crystal structure on its thermal expansion behavior. The crystal structure of brivaracetam form I was characterized by X-ray single crystal diffraction and variable temperature X-ray powder diffraction at different temperatures. The interaction energy of brivaracetam molecule calculated by B3LYP/6-31G(d,p) wave function with the aid of CrystalExplorer 21.5 software. The results show that brivaracetam form I exhibits significant reversible anisotropic thermal expansion under the temperature range of 123-323 K. The principal expansion X₁, X₂, X₃ axes are approximately aligned with the a, b and c axes of the unit cell, and the thermal expansion coefficients of the principal expansion axes are -127.61×10^-6, 95.96×10^-6, 233.80×10^-6 K^-1, respectively. The a-axis exhibits negative expansion characteristics. The volumetric thermal expansion coefficient is 202.17×10^-6 K^-1. The energy framework of the crystal is obvious layered, and the interaction energy between layers is weak, which leads to a significant linear positive expansion in the c-axis direction of the unit cell. Through a combination of experimental and theoretical methods, the thermal expansion characteristics of brivaracetam form I are systematically analyzed, and the influence mechanism of the crystal structure on its thermal expansion behavior is explored, which has certain guiding significance for the production process of tablet preparations in practice.