Exploring the potential of complex-vesicle based niosomal ocular system loaded with azithromycin: Development of in situ gel and ex vivo characterization

Abstract Bacterial conjunctivitis characterized as pink eye referred as an inflammation of an eye caused by the enlargement of blood vessels present in conjunctiva, resulting in a red or bloodshot appearance of the eyes. Topical ocular delivery is found to be useful in treating conjunctivitis, but to maintain an effective drug concentration at a site of action in order to achieve desired pharmacological action is highly challenging. Thus, keeping in mind this limitation niosomal carrier was designed to provide localized drug delivery with enhanced residence time. Thus, the present investigation was targeted to explore the utility of niosomes loaded with azithromycin-β-CD complex. Azithromycin-β-CD complex was prepared and niosomes containing this complex were developed based on ۳۲ full factorial design using ether injection method and characterized. Optimized niosomal formulation (NF۲) was selected on the basis of minimum vesicle size (۳۰۶ ± ۳.۰۵ nm), polydispersity index (۰.۱۱۵ ± ۵.۵۱), maximum zeta potential (۴۵.۳ ± ۰.۲۵ mv), entrapment efficiency (۷۸.۱۷ ± ۱.۸۱ %) and % CDR (۷۳.۰۹ ± ۲.۱۰). Optimized formulation was then formulated in the form of in situ gel (temperature sensitive) and evaluated. Optimized formulation [in situ gel (NG-۵)] was found to exhibit superior in vitro drug release profile in comparison to Zithromax® eye drop. Better in-vitro mucoadhesive strength was observed and formulation was found to be non-irritant to the sclera surface. Thus, it can be put into conclusion that temperature-sensitive niosomal in situ ocular gel possessed increased residence time and provide localized drug delivery effective for the treatment of bacterial conjunctivitis. Optimized niosomal formulation (NF۲) was selected on the basis of minimum vesicle size (۳۰۶ ± ۳.۰۵ nm), polydispersity index (۰.۱۱۵ ± ۵.۵۱), maximum zeta potential (۴۵.۳ ± ۰.۲۵), entrapment efficiency (۷۸.۱۷ ± ۱.۸۱ %) and % CDR (۷۳.۰۹ ± ۲.۱۰). Optimized formulation was then formulated in the form of in situ gel (temperature sensitive) and evaluated. Optimized formulation [in situ gel (NG-۵)] was found to exhibit superior in vitro drug release profile in comparison to Zithromax® eye drop. Better in-vitro mucoadhesive strength was observed and formulation was found to be non-irritant to the sclera surface. Thus, it can be put into conclusion that temperature-sensitive niosomal in situ ocular gel possessed increased residence time and provide localized drug delivery effective for the treatment of bacterial conjunctivitis.

Keywords:

β-CD , conjunctivitis , eye , penetration , residence time , vesicular carrier