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

Azithromycin is commercially available as eye drops in a dose of 0.5 % w/v. The major limitation of the conventional formulations is enhanced precorneal drainage, because of which frequent instillation is needed. Use of high drug concentration is also required which usually leads to pulse kinetics pattern of drug release. The efficacy of azithromycin as an antibacterial agent in ophthalmic delivery is limited by poor solubility and limited permeability. Due to limited solubility and permeability, the ocular bioavailability gets reduced (1). A large portion of drug when administered using eye drops is reported to undergo loss by lachrymation, nasolachrymal drainage, tear turnover and tear dilution. These losses resulted in poor ocular bioavailability. The delivery of drug to ocular region basically depends upon the type of disease to be managed i.e. intraocular infection and extraocular infection. Extraocular related infection commonly includes conjunctivitis, keratoconjunctivitis, corneal ulcers, etc. Extraocular bacterial infection requires an antibiotic treatment regimen, as treatment with antibacterial agent reduces the chances of complications associated with chronic conditions such as corneal perforations if remain untreated (2). The success of an antibacterial therapy depends upon achieving and maintaining the therapeutic drug concentration at optimum site of action for longer duration of time. Major limitation in maintaining extraocular infection is the lack of ability of the delivery system to provide long term therapeutic concentration in the extraocular region without compromising the intraocular region (3). The most suitable treatment of extraocular bacterial infection is topical therapy but has limited potential due to poor bioavailability at the site of action and due to constraints in ocular delivery (4). To conquer the problems associated with topical therapy of azithromycin, many novel delivery systems have been designed including suspension (5), films (6), ointments (7). These systems have drawbacks of blurred vision, no true sustained effect, may cause allergies with selective diseases, and poor patient compliance. Hence, present research is being undertaken to make use of βcyclodextrin complex encapsulated in vesicular system. Complexation of drug with βcyclodextrin will improve the solubility of azithromycin by forming complex with the drug (8). Drug delivered through the vesicles on the other hand will prolong drug delivery and provide SR/CR at the desired corneal region (9), by minimizing the systemic drainage and 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 3 full factorial design using ether injection method and characterized. Optimized niosomal formulation (NF2) was selected on the basis of minimum vesicle size (306 ± 3.05 nm), polydispersity index (0.115 ± 5.51), maximum zeta potential (45.3 ± 0.25 mv), entrapment efficiency (78.17 ± 1.81 %) and % CDR (73.09 ± 2.10). Optimized formulation was then formulated in the form of in situ gel (temperature sensitive) and evaluated. Optimized formulation [in situ gel (NG-5)] 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.