Formation of isostructural solvate forms of apremilast from the view of nucleation behavior

Apremilast (APM) is an antipsoriasis drug with a unique structural feature of easily forming isostructural solvates. In this study, a new APM isostructural solvate was prepared, known as Form E. In Form E, the solvated acetonitrile molecules with APM molecules form a sandwich structure in a 1:1 ratio, which is different from the stoichiometric amount of isostructural solvates containing aromatic solvents. Form E also has different thermal properties and structural features from the thermodynamically stable Form B. The induction time and nucleation parameters of Forms B and E were further determined, indicating that the solvent is selective for the nucleation of specific APM forms. Finally, the APM trajectories and nucleation behavior of Forms B and E were simulated by molecular dynamic simulations, confirming that the solvent effect can promote the selective nucleation of Form E by reducing the energy required for dimer formation in acetonitrile.<p></p>