Developing the Oxalate, Fumarate and Succinate Salts of Tetrabenazine: Solid-State Characterization and Solubility.

Abstract

Background: Tetrabenazine (brand name Nitoman and Xenazine) is a compound used to treat neurological and psychiatric disorders. Due to its low solubility, this drug is administered to patients in high doses, which produces side effects. Methods: To overcome these deficiencies, we prepared, using the mechanochemical method, three salts of tetrabenazine with three coformers: oxalic, fumaric, and succinic acid. The new solid forms were identified by X-ray powder diffraction (XRPD). Results: Full structural characterization was performed by single-crystal X-ray diffraction (SC-XRD), which revealed that the supramolecular interactions in the new solid forms were achieved by proton transfer between the coformer and the nitrogen of the tetrabenazine molecule. The salts formation was also evidenced by thermal analyses (DSC) and infrared spectroscopy (FTIR). Furthermore, the physical stability of the salts was evaluated under extreme temperature and humidity conditions. Conclusions: From a pharmaceutical perspective, UV-VIS tests of the new salts dissolved in water revealed a significant improvement in their solubility, which could improve their bioavailability in therapeutic applications.