Improving Lovastatin Absorption using Supersaturated-Self Nanoemulsifying Drug Delivery System (SNEDDS)

Lovastatin is a cholesterol-lowering agent has low bioavailability. Therefore, Supersaturated Self Nanoemulsifying Drug Delivery System (super-SNEDDS) can be used to increase bioavailability of lovastatin. This research aims to provide the formula for supersaturated-SNEDDS lovastatin. The selection of super-SNEDDS components is based on the solubility of lovastatin in various oils, surfactants, and cosurfactants. A pseudo-ternary phase diagram was created to determine the lower and upper limits of the oil (X1), surfactant (X2), and cosurfactant (X3). Super-SNEDDS optimization was carried out using a D-Optimal Mixture Design with response values in the form of percent transmittance and emulsification time. The optimum formula was confirmed and characterized including size of droplet, polydispersity index, zeta potential, physical stability, and in vitro absorption test using the small intestine-inverted method. The results showed the optimum formula consists of lovastatin (5,5 mg/gram SNEDDS preconcentrate), 5% oleic acid, 80% Tween 80, and 15% PEG 400. The optimum formula for super-SNEDDS had a droplet size of 18.07 nm, a polydispersity index of 0.34, and a zeta potential value of -228.9 mV. Lovastatin super-SNEDDS preparation was physically stable based on the stability test of the preparation at a temperature of 40°C and after freeze-thaw stability test cycles. The in vitro oral absorption using everted gut sac method showed that the cumulative amount of lovastatin absorbed in the lovastatin super-SNEDDS preparation was 1.6-fold higher than in the lovastatin SNEDDS preparation and 3.3-fold higher than in pure lovastatin.