Azithromycin and Dexamethasone Loaded β-glucan Films for the Treatment of Blepharitis

Abstract

Background and Aim: Blepharitis is considered as one of the most common ocular surface conditions in optometry and ophthalmology practice. It is classified anatomically into two types, anterior and posterior blepharitis. Due to its chronic nature, development of a controlled topical delivery system is desirable. Azithromycin is a macrolide antibiotic which is structurally derived from erythromycin and is used as a topical treatment for blepharitis, while dexamethasone has also been used in this condition to reduce inflammation. Currently, they are only available as a conventional eye drops which are associated with several problems including fast nasolacrimal drainage; therefore, controlled delivery systems are desirable. Ocular inserts are solid dosage forms that can be placed in the conjunctival cul-de-sac and are able to deliver drugs over prolonged periods of time. They should ideally be biodegradable and are therefore mainly composed of natural or synthetic polymers. β-glucan is a natural polysaccharide obtained from barley used as food additive and well known for its biological and nutritional applications, while hydroxypropyl methycellulose (HPMC) is widely used in ocular preparations due to its viscosity enhancing and mucoadhesive properties. This thesis aimed to develop an ocular insert of β-glucan and HPMC loaded with both azithromycin and dexamethasone for efficient treatment of blepharitis. Methods: Ocular inserts were prepared by the solvent-casting method with different polymer concentrations and were then evaluated in terms of their appearance, thickness, weight and pH. Films were also characterised for their mechanical and bioadhesive properties, while the compatibility between the drugs and polymers was examined using both Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The ability of the ocular inserts to provide controlled release of the drugs was assessed by an in-vitro release study of dexamethasone and an antibacterial assay for azithromycin. Results and Discussion: The appearance, weight and thickness of the ocular inserts were in the acceptable range; however, the surface pH of the produced inserts was relatively high which may lead to ocular irritation. Inserts showed a high mechanical strength with acceptable flexibility. Compatibility studies revealed some chemical interactions between drugs and polymers in all produced inserts. The in-vitro release of dexamethasone was relatively fast with 100% of the drug released within one hour. Azithromycin also showed fast release from the inserts achieving the MIC after only 5 min and maintaining its antibacterial activity for 24 hrs. Conclusion: Inserts containing β-glucan and HPMC successfully delivered both drugs for a longer period of time compared with conventional topical eye drops and could therefore be a novel treatment option for blepharitis.