In Situ Gelling System: A Comprehensive Review

In situ gelling systems are an innovative class of drug delivery formulations that undergo a sol-to-gel phase transition under physiological conditions, such as temperature, pH, or ionic strength, at the site of administration. These systems are administered as low-viscosity liquids, which transform into semi-solid gels upon exposure to specific stimuli, thereby providing prolonged residence time, sustained drug release, and enhanced bioavailability. This unique property makes them particularly suitable for ocular, nasal, oral, buccal, vaginal, rectal, dermal, and injectable routes, where conventional dosage forms often suffer from rapid clearance, low absorption, or poor patient compliance. Various stimuli-responsive polymers, including thermosensitive, pH-sensitive, and ion-activated polymers, enable precise gel formation and controlled drug release. Preparation methods include temperature-triggered, pH-triggered, ion-activated, enzyme-responsive, dual/multi-stimuli responsive systems, and techniques such as spray-drying or freeze-drying. Evaluation parameters for these systems include visual clarity, pH, gelling capacity, viscosity, rheology, drug release, permeability, irritation, histological safety, sterility, and stability. Marketed formulations like Timoptic-XE®, Pilopine HS® Gel, and NasoGel® demonstrate their clinical utility. Recent advances focus on biodegradable polymers, nanocarrier integration, and tissue engineering applications. In situ gelling systems offer a versatile, patient-friendly platform for localized and systemic drug delivery, representing a promising approach to enhance therapeutic efficacy, reduce dosing frequency, and improve overall patient compliance in modern pharmaceutics.