Beyond the Blink: Using In-Situ Gelling to Optimize Opthalmic Drug Delivery

Abstract

Conventional ophthalmic solutions frequently show poor bioavailability and a weak therapeutic response because they are often eliminated before they can reach the cornea, when patients blink or their eyes tear. Use of in-situ gel forming solutions can help improve performance and patient compliance. These solutions are delivered as eye drops, but undergo a sol-gel transition in the conjunctival sac (cul de sac). This article describes how an ion-activated in-situ gelling system was designed to deliver an ophthalmic formulation of the antibacterial agent, Levofloxacin. The delivery system uses gellan gum, a novel ophthalmic vehicle that gels in the presence of mono or divalent cations in the lacrimal fluid. This gum was used alone, and combined with sodium alginate as a gelling agent and hydroxypropyl methylcellulose (HPMC) Methocel F4M as a viscosity enhancer. A 32 full factorial design approach was used, with two polymers: Gelrite and HPMC, as independent variables. Gelling strength, bioadhesion force, rheological behavior, and in-vitro drug release after 10 h were selected as dependent variables. Both in-vitro release studies and rheological profile studies indicated that the combined Gelrite–HPMC solution retained the drug better than the gellan gum alone or a combination of gellan gum– alginate–HPMC. The developed formulations were therapeutically efficacious and provide sustained release of the drug over a 12-h period in vitro. These results demonstrate that the Gelrite–HPMC Methocel F4M mixture can be used as an in-situ gelling vehicle to enhance ophthalmic bioavailability and patient compliance.