Formulation Development and Evaluation of Immediate Release Fixed Dose Combination of Anti-Hypertensive Agents

Abstract

The occurrence of hypertension is high in the patients with different of diseases like diabetes mellitus, chronic kidney disease and chronic cardiovascular disease. In addition, these subjects have the lowest control of blood pressure (BP) among the hypertensive patients and also the risk having a morbid or fatal cardiovascular event>20% in 10 years. For these reasons, the aggressive control of BP to <130/80 mm Hg for these subjects is strongly recommended by National and International guidelines. To achieve this goal, combination therapy is used with two or more anti hypertensive drugs with a complementary mechanism of action is necessary. Drugs that block renin-angiotensin system RAS (Angiotensin II Type 1 receptor blockers) in combination with a calcium channel blocker (CCB) have been shown to be the most effective combinations. Several studies have shown that patient compliance is related to the number of drug is administered. Sometimes, multiple drugs given separately decrease patient compliance and adherence to the treatment. To overcome these problems, different dual and triple drug fixed dose combination of Anti-hypertensive drugs being administered. Which are effective, safe and well tolerated by the patients. Here, the combination of class I and class II drugs are formulated and developed by using two different methods such as Wet Granulation method & Dry Granulation method. In which the different concentration of binders, disintegrants and solubilizers were added into intragranuler part or extragranuler part. In the coating of tablet, OPADRY ® Orange (HPMC Based) was used. The coated tablets were evaluated for assay, weight variation, disintegration time, % friability, hardness, drug content and in vitro drug release. The formula was optimized to generate the formulation which gives same drug release profile as that of innovator formulation. Thus the final formula was optimized for effective fixed dose combination of Anti-hypertensive agents.