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

Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202206293. doi: 10.1002/anie.202206293. Epub 2022 Aug 17.

Abstract

We present SpeedMixing, a rapid blending technology, as an approach for fast mechanosynthesis and discovery of model pharmaceutical cocrystals through rapid spinning in the absence of bulk solvents and milling/grinding media. Syntheses of pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, as well as controllable 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 extensive screens over 20 years.

Keywords: Cocrystals; Crystal Engineering; Green Chemistry; Mechanochemistry; Solid-State Chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbamazepine / chemistry
  • Crystallization / methods
  • Methanol*
  • Niacinamide / chemistry
  • Pharmaceutical Preparations
  • Saccharin* / chemistry
  • Solvents / chemistry

Substances

  • Pharmaceutical Preparations
  • Solvents
  • Niacinamide
  • Carbamazepine
  • Saccharin
  • Methanol