Cocrystallization and coamorphization are similar yet independent approaches toward modifying various pharmaceutically relevant properties of modern drug compounds, in particular, solubility, dissolution rate, and the associated bioavailability. In this work, both strategies were applied to enzalutamide (Enz), a poorly soluble nonsteroidal antiandrogen drug, which led to the development of new multicomponent crystalline and amorphous solid forms of the drug with saccharin (Schr) in a 1:1 molar ratio. The structural analysis of the cocrystal formed by Enz and Schr revealed multiple intermolecular interactions between the components. Both Enz···Enz and Schr···Schr interactions were observed in the crystal packing. With the aid of N-H···O, C-H···O, C-H···N, and C-H···S hydrogen bonds, the molecules were aggregated into a three-dimensional hydrogen-bonded network. In the coamorphous composition, however, the components do not seem to involve in any strong intermolecular interactions and undergo recrystallization separately upon storage at room and elevated temperatures. The thermodynamic solubility of the cocrystal, evaluated using eutectic concentrations of the components, was found to be higher than that of the parent enzalutamide over an entire range of physiological pH values. The advantages and drawbacks of both formulation methods were analyzed and discussed, taking into account a tradeoff between physical stability and dissolution performance of the considered coamorphous composition and the cocrystal.
