Solid-state versatility in tranexamic acid drug: structural and thermal behavior of new salts and cocrystals

Abstract

Tranexamic acid (TNA) is an anti-fibrinolytic hemostatic drug widely used in various medical treatments. Six new salts and five cocrystals of TNA are reported here and the crystal structures of the obtained multicomponent compounds were determined using single-crystal X-ray diffraction (SC-XRD) techniques. TNA formed salts with coformers maleic acid (MEA), nicotinic acid, DL-mandelic acid and saccharin. Salt formation with MEA resulted in three different solid forms, namely TNA–MEA (1:1), TNA–MEA (2:1) and TNA–MEA–H2O (1:1:1). All synthesized TNA salt structures were crystallized as anhydrous except for TNA–MEA–H2O (1:1:1). TNA formed cocrystals with phenolic coformers such as catechol (CAT), resorcinol, hydroquinone, pyrogallol (PRG) and phloroglucinol. All cocrystal structures crystallized as hydrates except for TNA–PRG (1:1). The detailed structural investigation using SC-XRD revealed the presence of robust N—H...O and O—H...O hydrogen bonds in TNA salts and cocrystals. In TNA cocrystals, except for TNA–CAT–H2O (1:1:1), the coformer molecules interact with TNA molecules via bridged water molecules. In all the salt structures, TNA exists as cations, in which both carboxylic and amino groups are protonated (–COOH and –NH3 +), while in cocrystals TNA exists as zwitterions with total charge zero. All synthesized multicomponent compounds were further characterized by differential scanning calorimetric, thermogravimetric and Fourier transform infrared analyses, and the formation of new multicomponent compounds were assessed based on the melting temperatures, percentage weight loss and stretching frequencies, respectively, corresponding to TNA/coformer molecules. A powder X-ray diffraction study confirmed the bulk purity of the synthesized crystalline multicomponent compounds.