2018-06-01T00:00:00Z, Ozdemir, Samet, Celik, BURAK, Sumer, Engin, Acar, Ebru Turkoz, Uner, Melike, ÇELİK, BURAK

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.

2018-06-01T00:00:00Z, Ozdemir, Samet, Celik, BURAK, Acar, Ebru Turkoz, Duman, Gulengul, Uner, Melike, ÇELİK, BURAK

Nanoemulsions of eplerenone (EP) were designed with the aim of improving its bioavailability for an effective antihypertensive therapy. Nanoemulsions were prepared by high shear homogenization and ultrasonication methods. Oleyl erucate, Brij (R) 35, Tween (R) 80, Tego Care (R) 450 and Poloxamer (R) 407 were used as the liquid lipid and surfactants for optimization of formulations by design of experiments approach. Thus, oil, surfactant and water contents of nanoemulsions were defined by determination of their droplet size and droplet size distribution by dynamic light scattering method. Formulations were screened by scanning electron microscopy. Drug payload and release properties of the formulations were investigated. Analytical quantification method of EP was validated by high performance liquid chromatograpy. Nanoemulsions having average droplet size between 150.6 nm and 205.8 nm were gained with homogenous droplet size distribution and high entrapment efficiency (84.47-98.51%). Formulations released 44.37-82.87% of EP within 1 h and drug release was completed up to 5-6 h. Thus, drug release characteristics of formulations optimized in this study might introduce benefits for rapid response and maintenance of treatment in hypertension attacks. As a result, design of experiments approach provided accurate and consistent datum with those obtained from experiments on the bench for optimization of formulations.