Abstract
Because Eplerenone (EPL) is a Biopharmaceutical Classification System (BCS) class-II drug and is prone to extensive liver degradation, it suffers from poor bioavailability after oral administration. This work aimed to prepare liquisolids loaded with EPL-nanoemulsions (EPL-NEs) that have a higher drug release rate and improved bioavailability by the oral route. Based on solubility studies, mixtures of Triacetin (oil) and Kolliphor EL/PEG 400 surfactant/co-surfactant (Smix) in different ratios were used to prepare EPL-NE systems, which were characterized and optimized for droplet size, zeta potential, polydispersity index (PDI), and drug content. Systems were then loaded onto liquisolid formulations and fully evaluated. A liquisolid formulation with better drug release and tableting properties was selected and compared to EPL-NEs and conventional EPL oral tablets in solid-state characterization studies and bioavailability studies in rabbits. Only five NEs prepared at 1:3, 1:2, and 3:1 Smix met the specified optimization criteria. The drug release rate from liquisolids was significantly increased (90% within 45 minutes). EPL-NE also showed significantly improved drug release but with a sustained pattern for four hours. Liquisolid bioavailability reached 2.1 and 1.2 relative to conventional tablets and EPL-NE. This suggests that the EPL-NE liquisolid is a promising oral delivery system with a higher drug release rate, enhanced absorption, decreased liver degradation, and improved bioavailability.
Highlights
Eplerenone (EPL), a member of the spironolactone group, is a new selective steroidal anti-mineralocorticoid receptor blocker
NEs are lipid formulations that can pass through the gastrointestinal tract (GIT) membranes and bypass liver degradation due to lymphatic absorption, which significantly enhances the bioavailability of poorly soluble drugs, especially those that suffer liver metabolism
EPL as a Biopharmaceutical Classification System (BCS) class II drug model that normally suffers extensive liver degradation was formulated into an NE using Triacetin and Kolliphor EL/Poly ethylene glycol 400 (PEG 400) (Smix) in different ratios
Summary
Eplerenone (EPL), a member of the spironolactone group, is a new selective steroidal anti-mineralocorticoid receptor blocker. EPL selectively prevents aldosterone receptor binding in both epithelial and non-epithelial tissues that results in the blockage of the renin-angiotensinaldosterone-system (RAAS), with subsequent inhibition of sodium reabsorption that affects blood pressure and the cardiovascular system [1,2,3]. EPL is used to treat hypertension, central serous retinopathy, and chronic heart failure either alone or in combination with other antihypertensive agents [6,7,8]. EPL helps to reduce the acute myocardial infarction death rate in patients with systolic dysfunction of the left ventricle and heart failure [10,11]
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