Formulation Development and Bioavailability Evaluation of a Self-nanoemulsifying Drug Delivery System (SNEDDS) of Atorvastatin Calcium

The main purpose of the present investigation is to enhance the solubility and bioavailability of poorly watersoluble atorvastatin calcium (ATR) through the self nanoemulsifying drug delivery system (SNEDDS).The components for self-nanoemulsion were identified by solubility studies and tendency for self-emulsification in various excipients. Sefsol 218, Cremophor RH 40 and Propylene glycol were selected as oil, surfactant and cosurfactant respectively. Pseudoternary phase diagrams were plotted to identify the efficient self-emulsification regions . Prepared SNEDDS formulations were tested for nanoemulsifying properties including robustness to dilution, visual assessment of self-emulsification, viscosity, drug content, droplet size and zeta potential. The SNEDDS formulation F3consist of 20% (w/w) Sefsol 218, 40% (w/w) Cremophor RH40 and 40% (w/w) Propylene glycol of each excipient showed the highest drug content (96.58%) and a small mean droplet size (12.7±0.3 nm) ,was selected as optimized SNEDDS formulation. For in vitro dissolution studies, the ATR SNEDDS was then formulated into soft gelatin capsules. It showed a faster rate of drug release into the aqueous phase .The optimized formulation ATR soft gelatin capsules were then subjected to stability studies at 30 ± 2°C/65 ± 5% RH for a period of three months. The ATRloaded SNEDDS was compared with the suspension of commercial tablet by oral administration in wistar rats. The bioavailability of ATR SNEDDS was significantly enhanced compared with that of the tablet (p<0.05).It was concluded that the potential use of the SNEDDS can improve the dissolution and oral bioavailability of lipophilic drug ATR. Keywords-Self-nano emulsifying drug delivery system (SNEDDS), atorvastatin calcium, ternary phase diagrams, droplet size, dissolution, oral bioavailability.