Solvent inclusion by the anti-HIV drug nevirapine: X-ray structures and thermal decomposition of representative solvates

The preparation, X-ray crystal structures, and thermal analyses of five solvates of the non-nucleoside reverse transcriptase inhibitor Nevirapine are reported. Thermogravimetric traces for the solvates indicated the following compositions (N = nevirapine): N center dot(ethyl acetate)(0.5) (1), N center dot(dichlorometharie)(0.5) (2), N center dot(toluene)(0.5) (3), N center dot(water)(0.5) (4), and N center dot(1,4-dioxane)(1.5) (5). Centrosymmetric, hydrogen-bonded nevirapine dimers occur in the crystals of 1-3 and in a previously characterized, unsolvated form of the drug 6. In crystals of 4, drug molecules are linked by a single N-H center dot center dot center dot O=C hydrogen bond only, whereas solvate 5 contains noncentrosymmetric nevirapine dimers. Solvent molecules in 1-3 occupy channels, whereas the water molecules in 4 occupy isolated sites and 1,4-dioxane molecules in 5 occupy layers. These inclusion modes are described with reference to the thermal behaviors of the solvates recorded in TGA and DSC.