Solubility, crystallization process optimization, and thermal properties of afoxolaner and the single-crystal structure of its hydrate

Abstract

As an emerging isoxazoline insecticide, afoxolaner has a good effect in the prevention and treatment of canine parasite infections. During the crystallization process of afoxolaner, inconsistent crystal phases and thermal properties are observed in the same batch of samples. In this work, the solubility and crystallization process were studied, and the best method was found to be slow evaporation in ethanol. The results showed that the crystal phase was highly consistent. The average peak value of DSC was observed at 149.6 ± 0.6 °C, with a relative mean deviation of only 0.4%. Furthermore, the isolation of needle-like single crystals allowed for the determination of the crystal structure, revealing the enantiomeric pairs of afoxolaner co-crystallized with water in a monoclinic crystal system belonging to the centrosymmetric space group P2₁/n. It is hoped that this study will provide important insights into the crystallographic data of afoxolaner for its practical applications.