Simvastatin in ternary solid dispersion formulations: Improved In vitro dissolution and anti-hyperlipidemia efficiency

Abstract

Simvastatin (SIM), an anti-hyperlipidemic agent, has poor solubility and dissolution rate, resulting in low bioavailability after oral administration. The present study aimed to enhance the dissolution rate of SIM by ternary solid dispersion formulation and therefore to improve its anti-hyperlipidemic effect.Solid dispersions (SDs) with various ratios of drug, polymer, and surfactant were prepared by the solvent method and evaluated for dissolution, solubility, and solid-phase characterization, including FT-IR, DSC, and XRD. Hypolipidemic activity of SD was determined in comparison with SIM powder and relevant physical mixture in hyperlipidemic rats. The serum samples were analyzed for total cholesterol, triglycerides, and high-density lipoprotein by the commercial diagnostic kits.Among the four types of tested surfactants, formulations containing Myrj 52 showed better results in terms of dissolution and solubility studies. In vitro dissolution studies revealed an enhancement of the dissolved SIM up to approximately 100% after 30 min. Moreover, in vivo experiments demonstrated that SIM-loaded ternary SD notably reduced total cholesterol and triglycerides in hyperlipidemia induced by a high-fat diet for two weeks. It can be concluded that developing ternary solid dispersion would be a practical approach for enhancing the dissolution and in vivo efficiency of SIM.