New organic salts of the antihypertensive drug hydralazine and their enhanced properties

Hydralazine (HDZ), a vasodilator widely used for the treatment of hypertension, has recently gained renewed attention due to its emerging pharmacological activities, including demethylation and antioxidant effects. Despite its decades-long history, HDZ has been commercialized exclusively in the form of hydralazine hydrochloride, which suffers from limitations such as low permeability and poor bioavailability. In this study, six novel salts of HDZ were synthesized and characterized to explore their potential as superior solid forms with improved physicochemical properties for hypertension treatment or other applications. Comprehensive analyses, including single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and thermal analysis, were performed to confirm the structures and properties of these salts. Additionally, their equilibrium solubility, intrinsic dissolution rates, and oil-water partition coefficients were evaluated. Among the new salts, HDZ-OA and HDZ-PA demonstrated significantly higher solubility and dissolution rates compared to hydralazine hydrochloride, while HDZ-MA and HDZ-GA exhibited superior lipophilicity. These findings suggest that the newly developed salts offer promising potential as improved solid forms of HDZ.