SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media. (17th August 2022)

• Record Type: Journal Article
• Authors: Teoh, Yong; Ayoub, Ghada; Huskić, Igor; Titi, Hatem M.; Nickels, Christopher W.; Herrmann, Brad; Friščić, Tomislav
• Is Part Of: Angewandte Chemie. Volume 134:Number 41(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-17
• Subjects: Cocrystals -- Crystal Engineering -- Green Chemistry -- Mechanochemistry -- Solid-State Chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202206293
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : The use of SpeedMixing, a rapid blending technology, for rapid and scalable synthesis and discovery of pharmaceutical cocrystals without using either bulk solvents or milling media is reported. SpeedMixing permits selective synthesis of cocrystal polymorphs, stoichiomorphs and revealed the first solvate of the archetypal pharmaceutical cocrystal of carbamazepine and saccharin, that has remained unknown despite 20 years of research and screening.