Advances in in-situ Gels for Ophthalmic Drug Delivery: Formulation Aspects, Mechanisms of Drug Release, and Therapeutic Application

In situ gels have become a promising approach for ophthalmic drug delivery because they overcome the major limitations of conventional eye drops, such as rapid drainage of the drug, poor bioavailability, and poor patient compliance. These formulations are liquid before administration and undergo sol-gel transition in response to ocular stimuli such as temperature, pH, or tear ions, thus extending the time of precorneal residence and allowing controlled release. This review summarizes the existing progress in the design and use of ophthalmic in-situ gels, with a special focus on their mechanistic basis, formulation parameters, and clinical progress. Ion-activated gellan gum systems, such as the marketed gel-forming solution of timolol, have shown clinical viability, while pH- and thermosensitive systems have shown promising preclinical and early clinical results. Recent developments have involved the incorporation of polymers with nanoparticles, hybrid gel systems, and new excipients to improve stability, ocular penetration, and patient tolerability. This article offers a contemporary review of the therapeutic potential of ophthalmic in-situ gels and the ability of these gels to enhance the management of pathologies such as glaucoma, dry eye disease, and ocular infections by synthesizing evidence from preclinical and clinical research.