Development and Evaluation of Sustain Release Simvastatin Pellets

Abstract

The aim of the present study is to develop and evaluate sustained release simvastatin pellets for the treatment of hyperlipidemia. This disease directly depends upon circadian rhythm of the body i.e. the maximal cholesterol synthesis is generally higher during the night. The activity of rate limiting enzyme HMG-CoA reductase is higher in the night time. Simvastatin an HMG CoA reductase inhibitor requires frequent dosing due to the lower bioavailability and shorter half life. The sustain release simvastatin pellets can be taken before bed time and capable of releasing drug after predetermined lag time. Simvatstain pellets were developed by the extrusion spheronization technique. The simvastatin pellets were prepared by using blend of microcrystalline cellulose (MCC), lactose, crospovidone and polyvinyl pyrrolidone (PVP K-30). The process variables such as spheronizing speed, amount of spheronizing aid (MCC) and binder (PVP K-30) were optimized and reported. The obtained pellets were subjected for determination of percentage yield, hardness, physicochemical properties and particle size analysis. The prepared pellets were further coated with ethyl cellulose as release rate retardant polymer, using fluidised bed processor by Wurster technique. Increasing the level of the ethyl cellulose coating retarded the water uptake and thus prolong the lag time for release of drug. The 30 % ethyl cellulose coating gave least release in 0.1 N HCl containing 0.5% SLS in 2 hours, in next four hours 97.4 % release was observed in Phosphate buffer.