Bioavailability enhancement of poorly soluble drugs with the approach of self-emulsifying drug delivery systems

PURPOSE: Eplerenone (EPL) is the second aldosterone antagonist registered for usage in the USA. It is utilized for the cure of heart failure, hypertension, and ventricular-systolic dysfunction. EPL is considered a class II medication, as it has poor solubility - high permeability. Our purpose in this study is to increase the solubility of EPL by using a self-emulsifying drug delivery system (SEDDS) and then solidifying it to form nanoparticles to be compared with the marketed and pure powder through in vitro dissolution studies. MATERIALS AND METHODS: Solubility studies were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for Eplerenone. After that, the ternary phase diagram was formed to conduct the perfect percentage for the primary three components (oil, surfactant, and co-surfactant) to determine the optimum SEDDS formulation composition. The solidification technique followed this procedure to increase the stability of liquid SEDDS and many more advantages. The solidification process was carried out with adsorption to solid carriers method by using FLO (calcium silicate), HPC (Low-substituted hydroxypropyl cellulose), Aerosil 200, and Neusilin US2. The prepared liquid and powdered SEDDS formulations were characterized and compared with the marketed product and pure drug of eplerenone. RESULTS: The solubility screening results showed high solubility of EPL in triacetin as oil, Kolliphor EL and tween 80 as surfactant and finally PEG 200, DMSO, transcutol p as co-surfactant and with ternary phase diagram optimum concentration of oil, surfactant and co-surfactant ratio have been determined. During the dissolution study, the results showed a remarkable increase in EPL dissolution rate (the entire dose in 30 minutes) when combined with S-SEDDS-F3 X compared to the marketed and pure drug powder (p < 0.05). CONCLUSION: Overall, this study approved that EPL's dissolution and oral bioavailability can be improved by SEDDS technology. Key words: SEDDS, S-SEDDS, Eplerenone, Solidification, Adsorption to solid carrier.