Effect of the Counterion on the Solubility of Isostructural Pharmaceutical Lamotrigine Salts

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 P2₁/c and P2₁/n space groups, being isostructural dicarboxylic acid salts of lamotrigine. Crystal structures of these salts are built up by hydrogen bond interactions of type N⁽⁺⁾−H···O⁽⁻⁾, N−H···O⁽⁻⁾, O−H···N, and N−H···O. The 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.