Sustained release timolol maleate loaded ocusert based on biopolymer composite

Highlights

• Timolol maleate loaded ocuserts was prepared using natural polymer sodium alginate.

• Significant reduction in IOP was observed within 3days.

• Prepared ocuserts proved to be a viable alternative over conventional marketed formulations for the treatment of glaucoma.

Abstract

In the present investigation, the effect of timolol maleate loaded ocuserts was studied as an alternative for conventional anti-glaucoma formulation. Ocuserts were prepared using natural polymer sodium alginate and ethyl cellulose. Physico-chemical properties along with drug entrapment efficiency (94–98%), content uniformity (93.1% ± 0.264–98.00% ± 0.321), in vitro drug release (83.42% ± 0.35 at end of 12 h), ex vivo permeation all showed satisfactory results, which was found to follow zero order kinetics. Ex vivo permeation studies showed better results, revealed that the permeability coefficient was dependent on polymer type. The sterility test accelerated stability studies and in vivo studies such as eye irritancy test, in vivo drug release of the optimized ocusert was determined. The anti-glaucoma activity was measured using Schiotz tonometer at different time interval. Significant reduction in Intra ocular pressure (IOP) within 3 days was observed in case of rabbits treated with ocusert in comparison to the rabbit treated with marketed eye drop formulation. Hence timolol maleate loaded ocuserts proved to be a promising and viable alternative over conventional eye formulation for the sustained and controlled ophthalmic drug delivery, targeting the drug within the ocular globe thus improving patient compliance for the treatment of glaucoma.

Introduction

Human eye is a sensitive spherical visual sense organ consisting of mainly cornea, sclera and retina. The accessory parts of eye include iris, pupil, lens, ciliary body, and conjunctiva. Worldwide, glaucoma is the second-leading cause of blindness after cataracts [1]. Glaucoma is a group of ocular disorders that result in optic nerve damage, often associated with increased fluid pressure in the eye Intraocular pressure (IOP) [2]. Glaucoma is an eye disease to ganglionic cells and optic nerves and left untreated leads to loss of vision and ultimately to blindness. The most conventional way of ocular delivery is using eye drops [3]. Only about 1–2% of instilled dose is absorbed into the target tissues and relatively concentrated solution is required for installation to achieve an adequate level of therapeutic effect, also the cornea which is the anterior most layers in eye acts as a strong mechanical barrier limiting the entry of exogenous substances [4]. The frequent periodic instillation of conventional eye drops becomes necessary to maintain a continuous sustained level of medication [5]. The potential of an anti glaucoma agent is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Novel drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. Ocuserts are having more patient compliance, ease of handling, stability, sterility and do not interfere with vision and oxygen permeability. They also increase the contact time and thus bioavailability, prolonged drug release, reduce systemic side effects, reduce number of administration, accurate dose administration and possibility of incorporating various novel chemical technological approaches such as pro-drugs, micro particulates, salts acting as buffers [6]. The drug delivered into the cul-de-sac gets absorbed by corneal route which mainly depends on the anatomical structure of cornea that further depends on the solubility nature of drug.The epithelial layer within the route is the rate limiting barrier for transcorneal diffusion of hydrophilic drug [7]. Absorption of drug also occurs across the non-corneal route by penetrating across the sclera and conjunctiva into the intra ocular tissue [8]. Thus the present work aimed to develop a matrix-dispersion type ocular drug delivery system of Timolol Maleate using blend of polymers having many advantages over conventional dosage form like increased ocular residence, possibility of releasing drug at a slow and constant rate, accurate dosing and thereby achieving better therapeutic action against an eye disease [9].