Optimization of β-cyclodextrin consolidated micellar dispersion for promoting the transcorneal permeation of a practically insoluble drug

• Published in: International journal of pharmaceutics 2018-10, Vol.549 (1-2), p.249-260
• Main Authors: Sayed, Sinar, Elsayed, Ibrahim, Ismail, Maha M.
• Format: Article
• Language: English
• Subjects: Adhesiveness; Administration, Ophthalmic; Animals; Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; Antifungal Agents - metabolism; Aspergillosis - drug therapy; Aspergillosis - metabolism; Aspergillosis - microbiology; Aspergillus niger - drug effects; Aspergillus niger - growth & development; beta-Cyclodextrins - chemistry; Cornea - drug effects; Cornea - metabolism; Cornea - microbiology; Cyclodextrin; Disease Models, Animal; Drug Compounding; Drug Liberation; Excipients - chemistry; Eye Infections, Fungal - drug therapy; Eye Infections, Fungal - metabolism; Eye Infections, Fungal - microbiology; Itraconazole; Itraconazole - administration & dosage; Itraconazole - chemistry; Itraconazole - metabolism; Keratitis; Keratitis - drug therapy; Keratitis - metabolism; Keratitis - microbiology; Male; Micelles; Ocular Absorption; Particle Size; Permeability; Rabbits; Solubility; Technology, Pharmaceutical - methods; Transcorneal
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.08.001

[Display omitted] Development of efficient ocular drug delivery system for antifungal drugs becomes a must nowadays to face and eradicate the widely spread ophthalmic fungal infections. Itraconazole, a triazole antifungal, is struggling to penetrate the cornea and subsequently, its efficacy is limited. The aim of this study was to enhance itraconazole corneal penetration through utilizing the minimum surfactant amount in presence of β-cyclodextrin which acted as a dissolution and permeation enhancer. β-Cyclodextrin consolidated micellar dispersions (CCMD) were prepared after an initial screening to select the composition of surfactant(s). The preparation was done according to a modified melt dispersion technique. The prepared CCMD were characterized through the analysis of their particle size, zeta potential and solubilization efficiency. The optimum formula was chosen based on a factorial response surface analysis and it was composed of 17:1 w/w surfactant/drug, 30:1 w/w cyclodextrin/drug ratios and 0.02% polyethylene oxide. This formula was subjected to in vitro characterization including release, imaging by transmission electron microscope, mucoadhesion, stability, in addition to the determination of the minimum inhibitory concentration. Moreover, the ex vivo/in vivo permeation, safety and efficacy profiles were determined. The optimized CCMD formula was found to be significantly safe, stable, mucoadhesive and efficient to permeate the drug through rabbits’ corneas. Consequently, the optimized CCMD formulation can be a promising, safe and efficient platform for the transcorneal delivery of lipophilic drugs including most antifungals.