Edaravone (EDR), a strong free radical scavenger, is known for its promising therapeutic potential in oxidative stress (OS) associated diseases, however poor oral bioavailability is the major obstacle in its potential use. Oral liquid dosage form is the most preferred delivery method in paediatric, geriatric and specialised therapies. The present research discusses the development of a Novel Oral Delivery System (NODS) of EDR to enhance oral bioavailability. From preformulation study, solubility, and stability were identified as key challenges and the requirement of an acidic environment and protection against oxidation were found to be critical. The NODS made up of a mixture of Labrasol (LBS) and an acidic aqueous system, was optimized on the basis of solubility and stability study. It can be stored ≤40°C for at least one month. Drug release from NODS was slow, sustained and significantly better as compared to suspension. The significant reduction in metabolism and improvement in permeability across the small intestine were observed with NODS compared to free EDR. The oral pharmacokinetic study showed 571% relative bioavailability with NODS compared to EDR suspension. From the results obtained, NODS is a promising candidate for use in OS associated diseases.
Keywords: Aqueous stability; Borneol (PubChem CID: 1201518); Edaravone; Edaravone (PubChem CID: 4021); Labrasol; Metabolism; Oral bioavailability; Permeability.
Copyright © 2016 Elsevier B.V. All rights reserved.