title: Ocular supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) to enhance econazole nitrate bioavailability.
abstract: Econazole nitrate (ECO) is a poorly water soluble antifungal drug. Having low aqueous solubility affects negatively its use for ocular treatment. This work aimed to prepare ocular supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) of ECO employing hydroxypropyl methylcellulose as a precipitation inhibitor to improve the drug solubility by avoiding its precipitation after administration. Various oils, surfactants and co-surfactants were used to construct SNEDDS. The SNEDDS were evaluated for globule size, polydispersity index and their irritation potential using hen's egg test-chorioallantoic membrane (HET-CAM). The best SNEDDS was loaded with ECO and HPMC to prepare S-SNEDDS. In-vitro precipitation test of the S-SNEDDS was done to study the effect of the precipitation inhibitor. ECO permeation in rabbits' eyes from the selected S-SNEDDS (with and without HPMC) was evaluated. The results showed that SNEDDS-X consisting of 20% Capmul(®) MCM C10 as an oil, 60% Cremophor RH40(®) as a surfactant and 20% Transcutol(®) HP as co-surfactant possessed the lowest PDI value and a non-irritant effect on the CAM. The in-vitro precipitation test showed that the use of HPMC successfully sustained the supersaturated state by avoiding ECO precipitation. Higher Cmax, AUC0-8 and longer tmax confirm the development of a successful ECO-loaded S-SNEDDS.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562 Cairo, Egypt. Electronic address: naaelkasabgy@yahoo.ca.
authors.forename: Nermeen Adel
authors.initials: NA
authors.lastname: Elkasabgy
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D011232:Chemical Precipitation; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems; D004464:Econazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D011817:Rabbits; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004655:Emulsions; D013501:Surface-Active Agents; D065347:Hypromellose Derivatives; D004464:Econazole; D008747:Methylcellulose
keywords: Econazole nitrate; Hen's egg test-chorioallantoic membrane; In-vitro precipitation test; Precipitation inhibitor; Supersaturated self-nanoemulsifying systems