Mechanochemical Synthesis of Pharmaceutical Salts

Besides synthesis of pharmaceutical co-crystals, mechanosynthesis has been successfully applied to the synthesis of pharmaceutical salts. Trask et al. have demonstrated mechanochemical screening for pharmaceutical salts by grinding the model API molecules trimethoprim and pyrimethamine with seven pharmaceutically acceptable carboxylic acids formic, acetic, maleic, fumaric, succinic, glutaric and salicylic. The results of screening experiments (Table 8.2) demonstrate that LAG is more versatile than neat grinding in screening for pharmaceutical salts. More importantly, the application of mechanochemical techniques not only led to the formation of already reported salt forms but also enabled the discovery of 14 new salt forms. 

Andre and co-workers have utilised kneading and neat grinding in the investigation of solvate and salt formation involving the small heterocycles dioxane, morpholine or piperazine and the API 4-aminosahcylic add. In particular, the use of mechanochemical approaches has led to the simple formation of solvate and salt forms that were otherwise obtained using more complex solution-based routes. 

CCDCf code of the known crystalline salt Neat Grinding LAG 

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