Development and Evaluation of Lipid based Formulation of Rosuvastatin

Abstract

Hyperlipidemia represents an acquired or genetic disorder that results in high levels of lipid in systemic circulation. These lipids tend to enter the walls of arteries and increase the risk of developing atherosclerosis leading to stroke or heart attack. Statins competitively inhibit HMG-CoA reductase enzyme and result in reduction of total cholesterol and LDL content, thereby preventing cardiovascular events by 30-35%. Rosuvastatin, a potent statin, is a valuable choice for first-line treatment in the management of low- to high-risk patients requiring lipid-lowering drug therapy. However, low aqueous solubility limits its oral bioavailability to only 20%. Therefore, development of lipid-based formulations to improve the drug solubility and thus bioavailability, would be an advantageous approach for effective management of hyperlipidemia. newlineRosuvastatin calcium was characterized and the test results were found to be in accordance with specifications given in Indian Pharmacopoeia 2014 and Certificate of Analysis provided by the manufacturer. Saturation solubility studies demonstrated pH-dependent solubility of rosuvastatin. Stability indicating assay method using RP-HPLC for estimation of drug in formulations was developed and validated as per ICH/USP guidelines. Bioanalytical method using LC-MS/MS was developed for quantitative estimation of drug in rat plasma with Atorvastatin calcium as the internal standard. All excipients used for formulation development were characterized as per their Pharmacopoeial standards and were found to comply with the specifications. Drug-excipient compatibility studies were performed at 40±2°C/ 75±5%RH in open vials for one month. None of the sample mixtures showed any form of incompatibility on physical observation and FTIR studies. newlineSelf-microemulsifying drug delivery system (SMEDDS) of rosuvastatin was developed by initially screening suitable oils, surfactants and co-surfactants with maximum drug solubility.