Formulation and Evaluation of Temperature Sensitive in situ Ocular Gel Drug Delivery System of Acetazolamide for the Treatment of Glaucoma

Background: Conventional eye formulations are generally flushed away from the lacrimal area due to the rapid elimination of drugs from this region, with only a small amount being absorbed. The short-term precorneal contact time, coupled with corneal impermeability, leads to decreased bioavailability, necessitating repeated instillation of drops. Therefore, there is an urgent need for a system that can address these issues, maintain sustained drug action and enhance effectiveness. Numerous attempts have already been made to develop a system that can sustain drug release, with in situ gels being one promising approach. Objectives: This study aimed to formulate and evaluate a temperature-sensitive in situ ocular gel drug delivery system for Acetazolamide (ACZ) to treat glaucoma, providing prolonged drug release. Materials and Methods: A temperature-sensitive ophthalmic in situ gel of ACZ was prepared using a cold method and temperature-dependent polymers. The prepared gel was assessed for its appearance, clarity, pH, gelling ability, gelling temperature, sterility, viscosity, exvivo permeation study, in vitro ocular irritancy test and in vivo pharmacodynamics study. Results: The ex vivo permeation study and in vivo pharmacodynamics study revealed that Formulation 3 exhibited the highest drug release. The formulation was found to be sterile. The in vitro ocular irritancy test (Hen's Egg Test-Chorioallantoic Membrane) confirmed that the formulation was non-irritating and the in vivo pharmacodynamics study on Wistar rats demonstrated that the formulation remained effective for an extended period. In situ gels extended the contact time and improved bioavailability, making them a promising approach for advanced drug delivery.