Temperature- and pH-responsive cetirizine hydrochloride in situ gels for enhanced ocular delivery in allergic conjunctivitis.

Cetirizine eye drops provide rapid symptom relief in allergic conjunctivitis but are limited by short precorneal residence and frequent dosing. This study aimed to develop and compare dual pH- and temperature-responsive in situ gels incorporating Poloxamer and two Carbopol grades to enhance ocular retention and improve therapeutic efficacy. Two formulations were prepared using Poloxamer 407/188 with either Carbopol AA-1 (AA-Gel) or Carbopol TR-1(TR-Gel). Sol-gel transition, microstructure, rheology, erosion, drug release, irritation, precorneal retention, and pharmacodynamic performance were evaluated. The two Carbopol grades generated distinct gel networks, with the TR- Gel forming thicker structural struts, exhibiting higher viscosity, greater resistance to dilution, slower erosion, prolonged precorneal retention, and more sustained cetirizine release. In vivo, the TR-Gel reduced scratching behavior, inflammatory cytokines, and histopathological damage compared to both the AA-Gel and commercial eye drops, without causing ocular irritation. The dual-responsive behavior and Carbopol-dependent network architecture enhanced the stability, retention, and pharmacodynamic performance of cetirizine in situ gels. The TR-Gel, in particular, shows promise as a patient-friendly and more effective alternative to conventional eye drops for managing allergic conjunctivitis.