Design, Optimization & In-Vitro Evaluation of Sodium Alginate Based Gastro-Retentive Floating In-Situ Gel Of Simvastatin in Hyperlipidemia Treatment

Abstract

Hyperlipidemia (Raised cholesterol levels) increases the potential risks of heart disease and stroke both in the developed and developing world.  Drug Simvastatin, is an antihypertensive agent used in treatment of hyperlipidemia. Simvastatin is a derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3-methyleglutaryl coenzyme is a lipid-lowering medication, with a very short biological half-life of 2 hours, it extensively goes in first pass metabolism. The aim of present investigation is to formulate, optimize & characterized novel gastro-retentive in-situ gel system of simvastatin to avoid challenges associated with rapid gastric transition from stomach & decrease the frequency of dosing with increase enough residence time in stomach. Different polymers like sodium alginate, methyl cellulose were screened at different concentration to finalized optimum formulation based on in-vitro gelling time with drug release behavior. All the batches (ASF1-ASF6) were evaluated for pH, viscosity, gel strength, in-vitro floating ability, drug content determination and in-vitro release studies. The gel strength was conducted in 0.1 N HCl with 1% SLS (pH-1.2). All the formulations showed good gel strength. Formulations ASF1, ASF3, ASF4.and ASF5 were best fitted to Zero order model while formulations ASF2, and F6 were best fitted to Korsmeyer-Peppas modelas evident from correlation coefficients. Formulation ASF3 was found optimized the release as per korsemeyer-peppas model and drug-release from the formulation can be best explained by Higuchi model due to highest value of R-square among all the models. It can be concluded that the In-situ gel was beneficial for delivering the drug which needs sustained release to achieve the slow action.
Key-words: Gastro-retentive in-situ gel system, Simvastatin, Hyperlipidemia, sodium alginate.