Office of Technology Transfer – University of Michigan

Reaction Cocrystallization of Molecular Complexes or Cocrystals

Technology #3180

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Nair Rodriguez-Hornedo
Managed By
Tiefei Dong
Senior Licensing Specialist, Life Sciences 734-763-5332


Cocrystallization is an essential processing step in the successful production of multi-component crystalline phases (cocrystals or crystalline molecular complexes of at least two components). The most generally applied techniques, crystallization by solvent evaporation, cooling solutions, and non-solvent methods, all suffer from the risk of crystallizing the single component phases thereby eliminating the possibility of accessing the multi-component crystalline phase. A cocrystalline product may contain pharmaceutical components or active pharmaceutical ingredients. There is a need for preparation of multi-component crystals that is both consistent and efficient.


University of Michigan researchers have created a novel and effective method for the synthesis of multi-component crystals by a reaction of the crystal components in solution, solid-liquid systems, or slurries. This process does not involve grinding, co-grinding, solvent evaporation, or temperature variation. This invention also provides effective screening methods to rapidly prepare multi-component crystals in micro-phases and macro-phases under ambient conditions, in aqueous and organic solvents, and can be used in batch and continuous cocrystallization processes. This method provides the ability to simultaneously synthesize cocrystals and control the particle size as well as the specific surface area of the cocrystalline product. It is applicable to the process of making pharmaceutical cocrystals where at least one of the cocrystal components is an active pharmaceutical ingredient. Also see UM Files 3457, 4274, 4415.

Applications and Advantages


  • Isolation and large-scale synthesis of pharmaceutically active cocrystals.


  • Ability to isolate multi-component-nl-crystalline phases.
  • Isolation in shorter time periods.
  • Production can be ramped up for large-scale-nl-manufacturing.