Solubility Measurement and Dynamic Simulation Analysis of the Brivaracetam Form A in 12 Pure Solvents

Presented are studies in which the solubility of the antiepileptic drug brivaracetam Form A was evaluated in 12 pure solvents through dynamic methods at different temperatures (from 278.15 to 328.15 K) under atmospheric pressures. The solubility of brivaracetam was found to increase with increasing temperature in all solvents, with the highest solubility observed in alcohols, followed by esters, ethers, and alkanes. Calculations were performed on the van der Waals forces between brivaracetam and the solvent molecules using molecular dynamics to elucidate the dissolution behavior of brivaracetam in various solvents. Further, the electrostatic interaction from the hydrogen bonding energy of brivaracetam in different solvents was calculated, and the sum of the van der Waals interaction and the electrostatic component of the hydrogen bond energy was proposed to explain and predict the solubility of brivaracetam in various solvents. The larger the value is, the greater the solubility will be.