Abstract

FORMULATION OPTIMIZATION AND EVALUATION OF SELF EMULSIFYING DRUG DELIVERY SYSTEM OF ATORVASTATIN CALCIUM BY USING DESIGN OF EXPERIMENTS

D. Akiladevi*, M. Nappinnai, A. Jerad Suresh, P.Amudha, T. Vetrichelvan

Abstract

The aim of the present research was to prepare, evaluate and optimize self emulsifying drug delivery system (SEDDS) of atorvastatin calcium of poor water solubility using design of experiment. A 13-run 32 full factorial design with 2 factors and 3 levels, including 4 replicates at the centre point, was used for fitting a 2nd order response surface. After preliminary screening, Sunflower oil, Labrasol as surfactant and Transcutol HP as Co surfactant were taken as independent variables. The dependent factors (responses) were particle size and percentage drug load. The responses were optimized simultaneously by using desirability function, and the results demonstrated marked main and interaction effects of independent factors on responses. The optimized formulation consisted of 67.586% (w/w) oil, 52.529% w/w Smix showed measured responses of particle size 169.7 nm, Percentage drug Load of 87.2%, polydispersity index of 0.2 and Zeta potential of -31.8 mV values. For the optimized formulation, predicted value and experimental value were in close agreement. The in vitro evaluation parameters such as emulsification time, viscosity determination, cloud point measurement, turbidity measurement, refractive index and spectroscopic optical clarity were measured. The in vitro drug release from optimized atorvastatin SEDDS formulation was found to be 99.75% after 90 minutes which was highly significant in comparison to the marketed tablet and pure drug. Drug release kinetic of optimized batch showed first order with fickian diffusion type drug release. The optimized formulation was stable at varied temperatures of stability study.

Keywords: Formulation, optimization, evaluation, design of experiments, atorvastatin calcium, self emulsifying drug delivery system.