Temozolomide Cocrystals with Carboxamide Coformers

Temozolomide (TMZ) is an antitumor prodrug of broad spectrum antineoplastic activity. TMZ is stable in acidic medium (pH 7). In continuation of our efforts to design stable cocrystals of TMZ with partners such as organic acids (pKa 2–5) and a salt dihydrate with hydrochloric acid, we report herein TMZ cocrystals with amide coformers, e.g., isonicotinamide, nicotinamide, pyrazinamide, p-hydroxybenzamide, saccharin, and caffeine. TMZ exhibits polymorphs in the p-hydroxybenzamide cocrystal (synthon polymorphism). The occurrence of the stable conformation A of temozolomide and metastable conformation B (energy difference 1.44 kcal mol–1) in amide cocrystals is compared with the overall statistics in temozolomide cocrystal structures and polymorphs. The novel cocrystals were characterized by spectroscopic, X-ray diffraction, and thermal methods.