Ocular supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) to enhance econazole nitrate bioavailability

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.

(1) ECO-loaded SNEDDS, (2) The egg's chorioallantoic membrane showing no irritation response after application of SNEDDS, (3) S-SNEDDS-A2 loaded (with HPMC 15cp) preserved the supersaturated state by avoiding ECO precipitation compared to S-SNEDDS-A (without HPMC 15cp) in phosphate buffer (pH 7.4) for 8 h, (4) Mean ECO concentration (±SD, n = 6) in tears following the administration of S-SNEDDS-A (without HPMC 15cp) and S-SNEDDS-A2 (with (HPMC 15cp) to six rabbits’ eyes.Figure optionsDownload high-quality image (104 K)Download as PowerPoint slide