Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs, but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using a related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole data set, there were trends within structurally related series of salts relating increasing melting enthalpy with increasing molecular weight of the counterion.
Ramirez, M., David, S. E., Schwalbe, C. H., Asare-Addo, K., Conway, B., & Timmins, P. (2017). Crystal Packing Arrangement, Chain Conformation, and Physicochemical Properties of Gemfibrozil Amine Salts. Crystal Growth and Design, 17(7), 3743-3750. https://doi.org/10.1021/acs.cgd.7b00352