Abstract

FORMULATION & DEVELOPMENT OF EXTENDED RELEASE METOPROLOL SUCCINATE AND IMMIDEATE RELEASE AMLODIPINE IN COMBINATION FORM

Abstract

Initiation of ß-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamic. Deleterious hemodynamic effects might be mitigated with the vasodilatation of combined calcium channel/ß-blocker therapy. This prospective, randomized study assessed the safety and efficacy of Metoprolol alone or combined with Amlodipine on hemodynamic parameters at baseline. Mean ejection fraction at baseline was 13.4% ± 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right a trial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure. There was no further measurable benefit with the addition of Amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and Amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment.

Keywords: Metoprolol Succinate, Amlodipine Besylate, Hydroxypropyl methyl cellulose (HPMC), Monolithic Matrix