Water Soluble Chitosan Mediated Voriconazole Microemulsion as Sustained Carrier for Ophthalmic Application: In vitro/Ex vivo/In vivo Evaluations

Abstract

Background: Voriconazole (VCZ) is a lipophilic candidate, effective against fungal infections like ocular keratitis and endopthalmitis. Objective: The purpose to develop, optimize and characterize voriconazole microemulsion as sustained medication for ophthalmic application. Methods: The pseudo-ternary phase diagrams were developed using oleic acid, isopropyl myristate and isopropyl palmitate (oil phases), tween 80 (surfactant), propylene glycol (co-surfactant), distilled water (aqueous phase) and modified chitosan (Mod.CH) as mucoadhesive polymer. The optimum composition of oil, Smix and water was selected on the basis of phase diagrams and as mucoadhesive polymer Mod.CH was used in the formulations. All the formulations were evaluated for thermodynamic stability/dispersibility, physicochemical parameters (droplet size, polydispersity index, zeta potential, drug content, viscosity, pH and conductivity), in vitro, ex vivo and in vivo studies. Results: All formulations showed droplet size below 250 nm, positive zeta potential and polydispersity index below 0.5. The in vitro drug release study performed on selected formulations showed maximum sustained release than marketed formulation. The in vitro transcorneal permeation experiment of formulations suggests that optimized formulations showed better permeation. The selected formulation of voriconazole microemulsion was able to produce maximum antifungal activity against Candida albicans when compared to marketed formulation. In vivo study performed on rabbit eyes, found more drug concentration in aqueous humor of optimized formulation; the AUC0→t of IPMVM-11 was approximately 6.84-fold higher than VOZOLE and efficiently enhanced the corneal bioavailability. Conclusion: The modified chitosan based on voriconazole loaded microemulsion was promising novel carrier for sustained action in ophthalmic medication.

Self-nanoemulsifying drug delivery system to improve transcorneal permeability of voriconazole: in-vivo studies

“…Bhosale et al found a higher VCZ corneal permeation with microemulsion containing IPM but their T max was observed at 4 h. This was ascribed to the synergy of the bioadhesive effect and the polycationic nature of the modified chitosan solution in their microemulsion formulation. [ 11 ]…”

“…This is not the case with conventional SNEDDS, which are diluted after contact with tear fluid as well as other nanoformulations such as microemulsions and solid lipid nanoparticles in which the amount of instilled surfactant is relatively high. [ 10,11 ]…”

Promising Antifungal Potential of Engineered Non-ionic Surfactant-Based Vesicles: In Vitro and In Vivo Studies

“…After the development of fungal infection, formulations (MCNNs) and marketed preparation (NTF (5% w/v)) were administered topically into the eye of rabbits. In each group that was infected with Candida albicans, the left eyes of rabbits served as control and were treated with sterile saline solution whereas MCNNs and NTF were administered to the right eyes (62). The eyes of each group were examined on days 0, 7, 14, and 21 for the status of healing, corner vascularization, iritis, hypopyon, and macular nebula.…”

Novel Ocular Drug Delivery Systems: An Update on Microemulsions

“…Finally, in vivo studies on rabbit eyes demonstrated that voriconazole was detected in aqueous humor and the corneal bioavailability was improved significantly. 84 Da Silveira et al aimed to develop amphotericin B-loaded ocular MEs by titration method. The toxicity of the MEs was assessed by in vitro toxicity assay against red blood cells and it was found relatively low.…”