Design and Development of Novel Synergistic Formulation of Pravastatin and Aspirin for the Treatment of Atherosclerosis and its Evaluation

Coronary artery diseases (CAD) represent a condition in which the blood supply to the heart muscle is partially or completely blocked. In atherosclerosis, the hardening of arteries occurs with decreasing elasticity of the arteries. For management of disease, cholesterol lowering agents like Pravastatin and anti-platelet agent like aspirin are commonly used. Various studies have shown that these agents when given in combination results in synergistic pharmacological activity, however they are not chemically compatible. In present work, formulation approaches utilizes principles of pelletization and coating technologies to form a stable drug delivery system. The enteric coating of the core aspirin pellets was done using Eudragit L 100 (6%) with polyethylene glycol 6000 (0.6%) till 2.5, 5 and 7.5 % weight gain was obtained. A barrier coating on enteric coated pellets was applied using hydroxyl propyl methyl cellulose (HPMC) 15 cps solution. For the layering of Pravastatin over the barrier coated pellets, Pravastatin was dispersed in 2.5% HPMC solution. The coating solution was sprayed over the pellets till a dose strength equivalent to 10 mg of Pravastatin per 250 mg of pellets was obtained. The optimized pellets were subjected to evaluation of drug content, bulk density, crushing strength, friability, size distribution, packing ability and in-vitro drug release, stability studies and in-vivo performance using trition X 100 induce hyperlipidaemia rat model. The developed formulation showed an effective cholesterol lowering effect as compared to standard marked formulation of Pravastatin. It indicates the development of stable combination formulation in which aspirin forms the enteric coated sustained release core and that of Pravastatin fast releasing outer layers of the pellets.