Understanding the thermal stability of apalutamide crystalline solvates through crystal structure analyses and computational studies

Apalutamide (APA) is a nonsteroidal antiandrogen (NSAA) drug used for prostate cancer treatment. The crystal structures of apalutamide–dimethylformamide (2 : 1 & 1 : 1), apalutamide–1,4-dioxane, apalutamide–N,N-dimethylacetamide, apalutamide–cyclohexanone, apalutamide–acetonitrile, apalutamide–acetone, apalutamide–2-butanol and apalutamide–ethanol were determined. Thermal analysis and lattice energy calculations were performed to understand the stability of the solvent molecules in the crystal structures. Characteristic amide catemer hydrogen bonding was observed in all structures except in the structure of the acetonitrile solvate, in which the amide N–H atom was bonded to the solvent molecule. In all the structures APA⋯APA and APA⋯solvent interactions were used to build a supramolecular hydrogen-bonded network in the crystal packing. The solvent molecules were involved in strong interactions with APA molecules and were seen to stabilize the crystal structures. Crystal packing similarity analysis revealed that the APA solvates show modest structural resemblance.