Crystal habit modification of the drug diflunisal that normally grows into extremely thin, long needles has been achieved by breaking the stacking effect with the help of co-formers. Eight new co-crystals are reported, along with three crystal structures. In all cases, ortho F disorder, often a feature in diflunisal structures was absent due to the presence of CH…F interactions. Co-milling diflunisal with oxalic acid produced 1:1 and 2:1 co-crystals. In contrast, in solution crystallisation oxalic acid played the role of an additive resulting in the crystallisation of diflunisal form I rather than form III. To rationalize co-crystal formation a statistical analysis of the CCDC data base for aromatic o-hydroxy carboxylic acids was carried out. All co-crystals of o-hydroxy carboxylic acids with the COOH dimer motif have an electron-withdrawing group on one of the acids. COOH…Nar motifs are formed preferentially over carboxylic homo-dimers in the presence of an Nar co-former. AbstractCrystal habit modification of the drug diflunisal that normally grows into extremely thin, long needles has been achieved by breaking the stacking effect with the help of co-formers. Eight new co-crystals are reported, along with three crystal structures. In all cases, ortho F disorder, often a feature in diflunisal structures was absent due to the presence of CH…F interactions. Co-milling diflunisal with oxalic acid produced 1:1 and 2:1 co-crystals. In contrast, in solution crystallisation oxalic acid played the role of an additive resulting in the crystallisation of diflunisal form I rather than form III. To rationalize co-crystal formation a statistical analysis of the CCDC data base for aromatic o-hydroxy carboxylic acids was carried out. All co-crystals of o-hydroxy carboxylic acids with the COOH dimer motif have an electron-withdrawing group on one of the acids. COOH…Nar motifs are formed preferentially over carboxylic homo-dimers in the presence of an Nar co-former.

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