Cocrystal and Coamorphous Solid Forms of Enzalutamide with Saccharin: Structural Characterization and Dissolution Studies

Cocrystallization and coamorphization are similar yet independent approaches toward modifying various pharma-ceutically relevant properties of modern drug compounds, in particular, solubility, dissolution rate, and the associated bioavail-ability. 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 EnzmiddotmiddotmiddotEnz and SchrmiddotmiddotmiddotSchr interactions were observed in the crystal packing. With the aid of N-HmiddotmiddotmiddotO, C-HmiddotmiddotmiddotO, C-HmiddotmiddotmiddotN, and C-HmiddotmiddotmiddotS 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.

Automated summary

Cocrystallization and coamorphization are two independent but similar approaches used to modify the physical properties of drug compounds. In this study, both methods were applied to the poorly soluble drug enzalutamide, resulting in the development of new multicomponent crystalline and amorphous solid forms. The cocrystal exhibited higher thermodynamic solubility, while the coamorphous form underwent recrystallization upon storage.