RESUMO
CONTEXT: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. OBJECTIVE: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. METHODS: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. RESULTS: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. CONCLUSION: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).
