Mechanochemically Driven Synthesis of Anticancer Cocrystals: A Case Study of Lenalidomide

The modulation of physicochemical properties through the discovery of new solid forms has attracted significant interest in the pharmaceutical industry. Herein, a novel cocrystal of lenalidomide with quercetin was designed upon crystal engineering principles. Bearing in mind the importance of developing sustainable methods for the pharmaceutical industry, the synthesis of the novel cocrystals was explored by different mechanochemical approaches and slurry techniques for comparison purposes. Thus, the cocrystal was produced by liquid-assisted grinding in ball milling, liquid-assisted resonant acoustic mixing, and the slurry method. All the methods yielded the same final form with similar properties. From the point of view of properties enhancement, solubility studies showed that the cocrystal exhibited lower solubility than that of pure lenalidomide under simulated conditions of gastric and intestinal fluids, suggesting that the cocrystal may function as an extended-release form of lenalidomide. Furthermore, this cocrystal remained stable under accelerated stability conditions, indicating that atmospheric relative humidity does not represent a risk for the handling or storage of these compounds in the solid state.