Eplerenone nanoemulsions for treatment of hypertension. Part II: Physical stability assessment and in vivo study

Abstract

The aim of the present complimentary study was to investigate physical stability of eplerenone (EP) loaded nanoemulsions and to evaluate their pharmacokinetic profiles after subcutaneous application to Sprague Dawley rats. Nanoemulsions were prepared by using high shear homogenization and ultrasonication techniques. All formulations were having 0.1% EP. They were obtained in 150.6 nm-205.8 nm size range. Physical stability of nanoemulsions was monitored storing them at different thermal conditions for 120 days. Droplet size was confirmed to be affected by storage temperature when it slightly changed at 4 +/- 2 degrees C and 25 +/- 2 degrees C. 40 +/- 2 degrees C was found not to be suitable as a storage condition in general. Pharmacokinetic study on physically stable formulations demonstrated that subcutaneously applied eplerenone solution showed that AUC(0)->infinity and C-max were 1.62 and 2.05 folds higher than eplerenone solution after oral administration. Additionally, AUC(0)->infinity and C-max were significantly increased in the case of nanoemulsions prepared with Brij (R) 35 and Tween (R) 80. Relative bioavailability of the drug was found to be remarkably increased after administration of formulations stabilized with Tween (R) 80. Results suggested that eplerenone loaded nanoemulsions may provide an alternative application way for efficient management of hypertension attacks.