T. Satyanarayana*1, K. Someshwar2
1Department of Pharmaceutics, Browns College of Pharmacy, Khammam, Telangana, India
2Managers, Formulation R&D, KP Labs (A Division of KDPL), Kothapet, Hyderabad, Telangana, India
A B S T R A C T
In the present research Rosuvastatin calcium immediate release tablets were formulated and evaluated. Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. Rosuvastatin calcium is highly susceptible to light, moisture and low pH environment. In acidic environment, it undergoes conversion into lactone through intramolecular esterification, which takes place between carboxylic acid and hydroxyl groups that are present on β and δ carbons in this compound. This phenomenon reduces the stability of the compound and lowers the shelf life. To prevent this basic agents are added to the formulation, which reverse the reaction and improve the stability. In the present work, different basic agents such as sodium bicarbonate, sodium alginate, tri-sodium citrate, disodium hydrogen phosphate, tri-calcium phosphate were used in the formulations whose aqueous solutions produce pH of nearly 8 to overcome the above problem. Initially rosuvastatin IR tablets were prepared by direct compression technique using different alkalizers. From dissolution profile in pH-6.6 citrate buffer, di-sodium hydrogen phosphate was found to be optimum alkalizer, which stabilizes the drug in the acidic environment of stomach to produce desired effect. But the above formulated batches showed higher release rate than marketed which may result in drug decomposition in stomach. In order to prevent it further batches are prepared by wet granulation. Out of 12 formulations, F12 is the most promising one as indicated by its F2 values both in the official medium and in the discriminating medium. The dissolution profile of the formulation F12 was found to have equivalent percentage drug release with that of the Innovator in the official medium. The stability studies on F12 and marketed product in HDPE container at 400C / 75 % RH for 2 months were conducted as per ICH protocol shown better dissolution profile in F12 than marketed product.
Keywords: Rosuvastatin, Immediate release tablets, Sodium bicarbonate, Sodium alginate, Tri-sodium citrate, Disodium hydrogen phosphate, Tri-calcium phosphate etc.