Abstract

DEVELOPMENT AND PHARMACODYNAMIC EVALUATION OF ROSUVASTATIN-LOADED NANOSTRUCTURED LIPID CARRIERS FOR ORAL ADMINISTRATION

Rajshekhar Agarwal*, H. Padmalatha Malthar, CH. Madhumathi and B. Chaitanya Reddy

ABSTRACT

Rosuvastatin calcium (ROS) is the choice of anti-hyperlipidemic agent having 18-20% oral bioavailability because of its poor aqueous solubility (log P 5.7) followed by extensive first pass metabolism. The prime motivation for this work was to develop first time nanostructured lipid carriers (NLCs) to enhance oral bioavailability of ROS via targeting through intestinal lymphatic transport system. Amongst various lipids stearic (solid lipid) and oleic acid (liquid lipid) were screened to prepare five different batches of ROS loaded NLCs by employing hot homogenization technique. It was observed from obtained results, as content of oleic acid increased from 0 to 30 % there was decrease in particle size with increase in zeta potential, EE % and DL %. Optimized batch of ROS-NLCs (F4) showed excellent results for all evaluated parameters. In vitro dissolution study proven the biphasic release pattern of ROS-NLCs. Surface morphology of ROS-NLCs was assessed by scanning electron microscope which revealed non spherical shape of particles. Fourier transform infrared (FTIR) studies concluded that there were no interactions between ROS and the lipids used for study. Differential scanning calorimetry, powder X-ray diffractometry studies confirmed that ROS was entrapped in the NLCs and crystalline form converted to amorphous form. Triton induced hyperlipidemic model was used for examing in vivo pharmacodynamic activity of ROS-NLCs, results of which was found to be highly significant than plain ROS suspension, making NLCs as a promising perspective for oral delivery of ROS. Accelerated stability studies showed that there was no significant change in the mean particle size, PDI and EE % after storage at 25 ± 2 °C / 60 ± 5 % RH for the period of three months.

Keywords: Lipoidal nanoparticles, Intestinal lymphatic targeting, Stearic acid, Oral bioavailability, High pressure homogenisation, Triton induced hyperlipidemic model.