Formulation and Evaluation of Nanoparticles of HMG CoA Reductase Inhibitor

Abstract

quotThe HMG-CoA reductase inhibitor drugs (statins) are the most extensively used to lower blood cholesterol for the prevention of cardiovascular disease. Pitavastatin calcium (PTV) is a relatively newly developed, potent molecule which has greater efficacy in reducing the bad cholesterol (LDL-C) compared to other statins. However, its poor water solubility restricts its clinical effectiveness. Hence, the present study was undertaken to develop Pitavastatin nanoparticles to enhance solubility and dissolution performance and thereby bioavailability of the poorly soluble drug. newlineThe PTV nanoparticle was developed by the emulsion solvent evaporation technique followed by freeze-drying. The formulation was optimized using the design of experiment approach. Spectroscopic and thermal evaluation of optimized nanoparticles were performed. The optimized nanoparticles were incorporated into the tablet and evaluated for its in-vitro dissolution and in-vivo pharmacokinetic behavior. newlineThe optimized PTV nanoparticles showed a significant improvement in the solubility of prepared nanoparticles by 58.95-fold in distilled water and 32.01-fold in phosphate buffer pH 6.8. Further, the nanoparticle-loaded tablets had showed significant high dissolution efficacy and low mean dissolution time compared to the conventional product. In-vivo pharmacokinetic study indicated a 1.76-fold improvement in oral bioavailability compared to the marketed tablet. newlineThis PhD thesis will help in the development of novel conventional oral formulation of Pitavastatin nanoparticles which can effectively be used in the treatment of hypercholesterolemia for better efficacy and clinical outcome. newlinequot newline newline