Isoniazid cocrystallisation with dicarboxylic acids: Vapochemical, mechanochemical and thermal methods

Cocrystallisation with a series of related compounds allows for the exploration of trends and limitations set by structural differences between these compounds. In this work, we investigate how the length of a dicarboxylic acid influences the outcome of cocrystallisation with isoniazid. We have performed a systematic study on the mechanochemical, thermal and solvent vapour-assisted cocrystallisation of aliphatic dicarboxylic acids (C₃-C₁₀) with isoniazid. Our results demonstrate that the rate of mechanochemical and vapour-assisted cocrystallisation depends on the acid chain length and shows alternation between odd- and even-chain acids. The results of thermal cocrystallisation showed that the eutectic melting temperatures of isoniazid-dicarboxylic acid mixtures follow the same trend as the melting points of dicarboxylic acids.