SpeedMixing: Rapid Synthesis and Discovery of Model Pharmaceutical Cocrystals without Milling or Grinding Media

We present SpeedMixing, a rapid blending technology, as an approach for the mechanochemical discovery and synthesis of model pharmaceutical cocrystals without the need for bulk solvents and milling/grinding media. The syntheses of well-known model pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, and selective synthesis of cocrystals, cocrystal polymorphs and stoichiomorphs, including the discovery of an unexpected methanol solvate of the archetypal cocrystal of carbamazepine and saccharin, which has eluded numerous and extensive screens reported over almost 20 years.