Combined synthetic and solubility aspects of orotate salt of bilastine

Bilastine (BLA) is an European Medicines Agency approved second-generation antihistamine drug used for the treatment of allergic rhinoconjunctivitis and chronic urticarial. The major disadvantage of Bilastine is its poor aqueous solubility. In the present work, the authors describe the novel salt of BLA with orotic acid (ORA) as a counter ion. ORA is a well-known molecule that exhibits important physiological functions and pharmacological characteristics. The newly formed salt is thoroughly characterized by various spectroscopic and thermal methods. The crystal structure determination by Single-Crystal X-ray Diffraction (SC-XRD) techniques revealed the proton transfer from ORA to piperidine nitrogen of BLA. The melting temperature of the obtained salt was found to be in between the melting of BLA and ORA and the salt is found to be thermally stable until melting based on DSC, TGA, and Hot-stage analysis. FT-IR spectroscopy depicts the formation of salt based on -C = O stretching frequencies of both BLA and ORA. A detailed synthetic method is established for the BLA-ORA salt by employing various approaches in different solvents. The solubility study in purified water (pH = 6.5) and 0.1 N HCl (pH = 1.2) showed an increase of 4 and 1.2 fold respectively when compared with pure BLA drug.(c) 2022 Elsevier B.V. All rights reserved.