Design and Development of Fixed Dose Combination of Simvastatin fast Dissolving and Aspirin Anteric Coated Capsules

Abstract

Fixed dose drug combinations (FDCs), are combinations of two or more active drugs in a single dosage form. Fixed ratio combination products are acceptable only when the dosage of each ingredient meets the requirement of a defined population group and when the combination has a proven advantage over single compounds administered separately in therapeutic range. The two molecules simvastatin and aspirin are the best treatment therapy for treatment of dyslipidemia in diabetic patients. But the problem with the combination therapy is their chemical incompatibility, due to which there occurs a problem of decreased bioavailability of statins and a degradation of the acetyl salicylic acid. Simvastatin, a lactone, is HMG-CoA reductase inhibitors, readily hydrolyzing in vivo and thereby preventing the synthesis of mevalonic acid and used in cholesterol reduction. It is a BCS class-|| drug with low solubility and high first pass metabolism, thereby its bioavailability is less than 5%. Hence, there was a need for the enhancement of its dissolution properties. Several approaches like micellar dispersion, ß-CD complexation, Gellucire 44/14 dispersion, PEG 6000 dispersion & PG liquid solid compacts, out of which the formulations containing PG showed desired properties. Hence, PG was selected for further trails and used as an agent in the formulation of Liquid Solid compacts. The compacts were evaluated for several parameters, mainly dissolution properties and the best batch was selected. Aspirin, is chemically 2-Acetoxy benzene carboxylic acid used in the relief of headaches and muscle joints, also has an application in the enhancement of platelet sensitivity, thereby used as a combination with statins for the treatment of dyslipidemia in diabetic patients. But, since NSAIDS have a common disadvantage of gastric ulceration, enteric coating of the aspirin molecule by Eudragit L- 100 55 was needed which would serve a dual purpose of preventing chemical interaction and gastric problems.