ORAL DELIVERY OF ROSUVASTATIN LIPID NANOCARRIERS: INVESTIGATION OF IN VITRO ANDIN VIVO PROFILEAbstract
Present study is a systematic approach to provide ‘proof of concept’ for effective oral delivery of Rosuvastatin lipid nanocarriers for treatment of hyperlipidemia. Rosuvastatin is a ‘Superstatin’ belonging to BCS class II having low bioavailability (20%). Development of lipid nanocarriers for oral delivery of rosuvastatin can be beneficial in enhancing bioavailability and providing sustained release. In the current work, Rosuvastatin lipid nanocarriers were developed using Precirol® ATO 5 as lipid carrier and Tween® 80as surfactant, employing solvent emulsification-evaporation method. Investigation of effect of shear rate, solution temperature and concentration of organic solvent as process parameters were studied. Three-level two-factor(32) experimental design was applied to study the effect of lipidand surfactant on percent entrapment efficiency and particle size. Complete characterization of optimized formulation such as particle size, zeta potential, entrapment efficiency, TEM and in vitro release profile was carried out. Lipid nanocarriers exhibited mean particle size 79.31±4.82 nm, entrapment efficiency 81.29±1.11% and zeta potential -6.89±3.29 mV. In vitro diffusion of ROS from lipid nanocarriers using dialysis bag diffusion method provided pH-independent drug release. Ex vivo intestinal permeability through chick ileum revealed improvement in apparent permeability coefficient due to lipid coated nano-sized particles. In vivo absorption of ROS from lipid nanocarriers resulted in about 4.41-fold increase in AUC0-last and 8.14-fold increase in mean residence time compared to plain drug. In gist, Rosuvastatin lipid nanocarriers are advantageous in reducing dose and drug consumption, by effectively providing sustained release, which will ultimately help in minimizing dose-dependent adverse effects.
D. Suares and B. Prabhakar *
Department of Pharmaceutics, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS, Vile Parle (West), Mumbai, Maharashtra, India.
04 June, 2016
21 July, 2016
02 August, 2016
01 December, 2016