Formulation and Evaluation of Simvastatin Solid Dispersions for Dissolution Rate Enhancement

Simvastatin (SIM) is a lipid lowering agent derived synthetically from a fermentation product of Aspergillus terreus. Simvastatin reversibly inhibit HMG-CoA reductase, which catalyzes a rate-limiting step in cholesterol biosynthesis. One of the major problems with this drug is its low solubility in biological fluids, which results into poor bioavailability after oral administration. Therefore, solid dispersions (SDs) of Simvastatin were prepared to increase its aqueous solubility using carriers such as lactose, urea. Simvastatin SDs was prepared in 1:1, 1:2, 1:3, 1:4 and 1:5 ratios of the drug to carrier (w/w). Solid dispersions were prepared by employing solvent evaporation and kneading methods. The prepared solid dispersion was evaluated for drug content, in vitro drug release studies and powder X-ray diffractometry. In vitro drug release profiles of all SDs were comparatively evaluated and also studied against pure Simvastatin. Faster dissolution was exhibited by solid dispersion prepared by solvent evaporation containing 1:4 ratio of Simvastatin: Urea. It was observed that kneading method was more effective than solvent evaporation. In vitro drug release studies revealed that there was progressive improvement in the drug release rate from solid dispersions systems compared to pure drug alone. The rate of drug release was depended on the type, ratio of drug to carrier and method of preparation of solid dispersions. The enhancement in dissolution rate of the drug may be due to increase in wettability, hydrophilic nature of the carrier and due to reduction in drug crystallinity.