FORMULATION & DEVELOPMENT OF EXTENDED RELEASE METOPROLOL SUCCINATE AND IMMIDEATE RELEASE AMLODIPINE IN COMBINATION FORM
*S. Ashutosh Kumar1, Manidipa Debnath1, Y. Indira Muzib2, J.V.L.N.Seshagiri Rao3, Saravanan J4, N SaiKrishna4
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
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