Opportunities and Challenges in Mechanochemical Cocrystallization toward Scaled-Up Pharmaceutical Manufacturing

Recently, pharmaceutical cocrystals have gained immense interest because of their potential to tune mechanical, pharmacokinetic, and physicochemical properties of active pharmaceutical ingredients (APIs) while keeping their therapeutic action intact. In this review, cocrystallization is raised as a viable strategy toward commercialized pharmaceutical manufacturing, where attention has been paid to solid-state cocrystal preparation methods and their opportunities and challenges in overall product and process development. A comparative study of cocrystallization in the form of mechanical energy is demonstrated with the aid of SELECT criteria to qualitatively evaluate the synthetic route selection of scalable mechanochemical cocrystallization methods. Remedies and alternatives for the challenges that arise in mechanochemical synthesis of cocrystals are presented in this review, highlighting the commercial perspectives of sustainable, eco-friendly, and less toxic mechanochemical methods.