Voriconazole-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve transcorneal permeability

• Published in: Pharmaceutical development and technology Vol. 25; no. 6; pp. 694 - 703
• Main Authors: Rasoanirina, Bakoliarisoa Nivomalala Voahangy, Lassoued, Mohamed Ali, Kamoun, Amel, Bahloul, Badr, Miladi, Karim, Sfar, Souad
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-07-2020
• Subjects: Animals; Antifungal Agents - administration & dosage; Antifungal Agents - metabolism; Cattle; Cornea - drug effects; Cornea - metabolism; Drug Delivery Systems - methods; Emulsions - administration & dosage; Emulsions - metabolism; mixture design; Mycotic keratitis; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Organ Culture Techniques; Permeability - drug effects; response trace; SNEDDS; transcorneal permeability; voriconazole; Voriconazole - administration & dosage; Voriconazole - metabolism; voriconazole; mixture design; SNEDDS; Mycotic keratitis; response trace; transcorneal permeability
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450.2020.1731532

The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween
®
80 and Span
®
80 as oil, co-solvent, surfactant and co-surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. Ex-vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement (p < 0.05) in apparent permeability coefficient (1.982 ± 0.187 × 10
−6 
cm/s) when compared to commercialized formulation (1.165 ± 0.106 × 10
−6 
cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.