In-Vivo Pharmacokinetic Evaluation Of Simvastatin Nanosuspension And Its Antihyperlipidemic ActivityAgainst High-Fat Diet-Induced Hyperlipidemia In Animal Model

Abstract

Simvastatin is a poorly water-soluble anti-hyperlipidemic drug with low bioavailability of 5% in its crystalline form. Formulators in the pharmaceutical sector face a difficult problem when it comes to the poorly soluble drug. The available standard techniques are ineffective to increase solubility; preferably in which drugs are poorly soluble in both aqueous and non-aqueous systems. There is currently a need for novel therapeutic techniques to improve simvastatin bioavailability. The present investigation was carried out to prepare simvastatin nanosuspension using polymer including soya lecithin, poloxamer 188, and poloxamer 407 by the method of high-pressure homogenization to increase the solubility and dissolution rate of simvastatin. The different formulation of simvastatin nanosuspension was subjected to pharmacokinetic studies using rabbit. The anti-hyperlipidemic activity of simvastatin nanosuspension was evaluated by using high-fat diet-induced Wistar rats. The serum cholesterol, triglycerides, LDL, VLDL, and HDL was measured. The simvastatin formulation (poloxamer 188) F6 showed a significant reduction in lipid profile than the standard drug simvastatin. The AUC and t_1/2 were remarkably increased in simvastatin poloxamer nanosuspension (F6) compared with standard drugs.  The results showed that the formulation F6 has better efficacy compared to the pure drug of simvastatin. Nanosuspension has shown a better and promising role to treat hyperlipidemia.