Once-Daily Sustained-Release Matrix Tablets of Metoprolol Tartrate : Formulation and In-vitro Evaluation

Abstract:

In view of increasing incidents of cardiovascular complications and the subsequent urgent need in the development of therapeutic agents, 2-(N- substituted)-3H-phthalazin-1,4-diones(3a-d) and 1-(N- substituted)2,4,5- trihydropyridazin-3,6-diones(4a-d) have been synthesized and characterized by spectral data. The title compounds were prepared by condensing substituted aryl hydrazides with either phthalic anhydride or succinic anhydride. The synthesized compounds have been screened for coronary vasodilator activity on the isolated rat heart at 10 μg concentration. Almost all the compounds have exhibited significant activity. The in vitro nitric oxide donor activity by Griess reagent has been studied to understand mechanism of action of these compounds. The compounds released nitric oxide significantly at 100 μmol, indicating the coronary vasodilatation produced by these compounds could be at least, partially due to release of nitric oxide.

Key words: phthalazines, pyridazines, antihypertensive, vasodilator, nitric oxide, Griess reagent