Design, formulation, and evaluation of in situ gelling ophthalmic drug delivery system comprising anionic and nonionic polymers

Abstract

Background: The significant problem in the ocular drug delivery is the attainment of optimal drug concentration at the site of action. Development of therapeutic agents that require repeated long-term administration is a driver for the sustained release drug delivery systems, to result in less frequent dosing, and less invasive techniques. Therefore, to overcome the anatomical barriers and ocular bioavailability constrains, a novel drug delivery system in situ gels have been developed. Materials and Methods: The in situ gelling system comprises gellan gum, an anionic polymer responsible for the ionic gelation. Methylcellulose a nonionic polymer contributes for the viscosity and gels at the body temperature. The formulation was characterized for clarity, appearance, pH, gelation time, drug content estimation, rheological evaluation, effect of sterilization on the viscosity, in vitro diffusion study, isotonicity testing, and ocular irritation testing. Results and Discussion: The developed formulations exhibited sustained release of drug over 8 h thereby increasing residence time of the drug. Sterilization caused no effect on viscosity of the formulation. Optimized formulation was selected on the bases of ability to form instant gel and with increased viscosity of gel with a slow and prolonged in vitro drug release pattern. The optimized formulation was found to be nonirritating with no ocular damage or abnormal clinical signs to the cornea, iris, and conjunctiva. Conclusion: Hence, the developed ophthalmic in situ gel by virtue of its prolonged corneal residence time and sustained drug release could be considered a viable alternative to the conventional eye drops in achieving enhanced bioavailability.

Keywords

• Draize test
• gellan gum
• in situ gel
• methylcellulose
• power-law model
• rheology