Formulation and evaluation of once a day dual component gastro retentive drug delivery system

There is about 15-30 % incidence of co-existence of hypertension and hypercholesterolemia in India. This has more than additive adverse impact on vascular endothelium which leads to cardiovascular diseases. Hypertension and hypercholesterolemia are major risk factors in pathogenesis of coronary heart disease. Due to this, the patients may require concomitant treatment with antihypertensive and hypo-lipidemic agents. The combination of antihypertensive (beta blocker) and antihyperlipidemic (statin) drugs are reported to reduce cardiovascular events and progression of dyslipidemic hypertension. The purpose of this study was to prepare a bilayer gastro retentive tablet of Metoprolol succinate and rosuvastatin calcium using direct compression technology and optimize the type and concentration of polymer and superdisintegrant to give good drug release profile in patient having hypertension with hypercholesterolemia. Rosuvastatin is a competitive inhibitor of HMG co-reductase, has half-life of 19 h and bioavailability 20 % favors immediate release while Metoprolol succinate is a β1-selective adrenergic receptor blocking agent and numbers of clinical trials have demonstrated the beneficial effects of Metoprolol therapy in heart failure, with decreased mortality due to both reduction in sudden death and death from worsening heart failure and it has half-life of 3 to 4 hours, and high stability and higher absorption window in acidic environment of stomach, favors development of sustained release floating formulation. The current investigation aims at development of safe, stable and efficacious dual component (bilayer) floating tablet formulation with differential release profiles of antihypertensive drug candidate (sustained release) and antilipidemic drug candidate (as fast release) component. A bilayer tablet was prepared in which, HPMC K100, K4M, K15M were used as gel forming agents while cross carmellose sodium, sodium starch glycolate and cross povidone alone used as a superdisintegrant. A sodium bicarbonate used as effervescent agent. The bilayer tablets were characterized by lag time, floating time, weight variation, drug content, dissolution profile and stability study. Best formulation F9, release 99.48% of Rosuvastatin calcium after 30 min and 96.6% of Metoprolol succinate after 12 hrs to achieve local therapy in the stomach, site-specific drug delivery reduces undesirable effects of side effects, reduced frequency of dosing with improved patient compliance and significant increase in bioavailability.