Examples of Pharmaceutical Co-crystal Synthesis and Screening Using Mechanochemistry

4 Examples of Pharmaceutical Co-crystal Synthesis and Screening Using Mechanochemistry 

The use of co-crystals to enhance the hydration stability of a solid API was first demonstrated for model APIs caffeine and theophylline by forming cocrystals with dicarboxylic acids. Co-crystallisation with oxalic, malonic, maleic and glutaric adds provided co-crystals based on the expected carboxylic acid-imidazole heterosynthon. In both cases, the co-crystal with oxalic acid demonstrated enhanced hydration stability compared to the solid APIs and did not transform into a hydrate even after seven weeks exposure to 98% relative humidity. Similar observations were also made in the case of analogous co-crystals of theophylline.  

Fragments of the crystal structures of (c) (artemisinin)2-(resorcinol) and (d) (artemisinin)-(orcinol) co-crystals.  

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