Salt formation is an approach to improve the physicochemical properties of the solid forms of an active pharmaceutical ingredient. As the anticonvulsant drug Lamotrigine presents low water solubility, a set of its salts with four different counterions has been obtained, and the influence of the counterion on the salt properties has been investigated. Lamotrigine salts have been obtained from succinic acid, fumaric acid, DL-tartaric acid, and saccharin. Powder samples of each salt have been characterized by infrared spectroscopy, powder X-ray diffraction, and thermal methods. Single crystal structures of four of these salts have been solved from single crystal X-ray diffraction data. The salts crystallized in P2 1 /c and P2 1 /n space groups, being isostructural dicarboxylic acid salts of lamotrigine. Crystal structures of these salts are built up by hydrogen bond interactions of type NThe water solubility of these salts has been determined and appears directly related to the solubility of the precursor acid. The isostructural nature of the studied salts allows connection of their properties with those of the counterion involved. The importance of the counterion solubility on the final solubility of the salts is rationalized considering their crystal structures.

The search for materials capable of storing small molecular species is experiencing a shift from solids with permanent porosity towards organic materials capable of the uptake and release of lowmolecular-weight guests. We demonstrate that a solid mixture of the pharmaceutical compound lamotrigine with a range of saturated and unsaturated 1,4-butanedicarboxylic acids, when in combination with a third molecule, can result in the formation of a family of isostructural materials involving a structurally persistent binary-host framework based on a hydrogen-bonded molecular salt of lamotrigine and the acid. A systematic study, based on mechanochemical screening, has revealed a remarkable robustness to subtle changes in the chemical functionality of the acid in that at least 12 different acids can be used in combination with lamotrigine to generate isostructural binary-host frameworks. Such robust isostructurality results in the important attribute that the shape, size and surface chemistry of the inclusion cavities can be fine-tuned by systematic variation of the substituents on the dicarboxylic acid.

Isostructurality in three-component crystals achieved by the combination of persistent hydrogen bonding motifs and solvent inclusion3