The driving forces triggering the formation of co-crystals under milling conditions were investigated by using a set of multicomponent competitive milling reactions. In these reactions, different active pharmaceutical ingredients were ground together with a further compound acting as coformer. The study was based on new co-crystals including the coformer anthranilic acid. The results of the competitive milling reactions indicate that the formation of co-crystals driven by intermolecular recognition are influenced and inhibited by kinetic aspects including the formation of intermediates and the stability of the reactants.
Keywords: X-ray diffraction; crystal engineering; kinetics; mechanochemistry; structure determination.
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