Ocular in Situ Gels: Development, Evaluation and Advancements

The ocular route of drug administration is regarded as one of the most challenging yet essential pathways for effective therapy, primarily due to the unique anatomical and physiological barriers of the eye. Conventional ophthalmic dosage forms such as eye drops and ointments suffer from rapid precorneal elimination caused by blinking, tear turnover, nasolacrimal drainage, and limited corneal permeability. As a result, these formulations exhibit short residence time on the ocular surface, leading to poor bioavailability and the need for frequent administration, which ultimately reduces patient compliance. To overcome these limitations, significant research efforts have been directed toward the development of novel ophthalmic drug delivery systems capable of prolonging drug residence time and improving therapeutic efficacy. Among these approaches, in situ gel-based delivery systems have gained considerable attention. In situ gels are administered as low-viscosity liquids that undergo phase transition into a gel upon exposure to ocular physiological conditions such as temperature, pH, or ionic strength. This transformation allows the formulation to remain in contact with the ocular surface for an extended period, thereby reducing drug loss and enhancing absorption. Recent advancements in ophthalmic drug delivery focus on integrating multiple formulation strategies to achieve sustained and controlled drug release. These systems not only increase the contact time of the formulation at the corneal surface but also slow down drug elimination, resulting in improved bioavailability and reduced dosing frequency. In situ gel systems have demonstrated promising potential in delivering a wide range of ophthalmic drugs, including antibiotics, anti-inflammatory agents, anti-glaucoma drugs, and antifungals. This review comprehensively discusses ocular in situ gel drug delivery systems, highlighting their formulation approaches, mechanisms of gelation, evaluation parameters, and therapeutic applications. Emphasis is placed on their advantages over conventional ophthalmic formulations and their role in enhancing ocular drug bioavailability and patient compliance