Formulation and Evaluation of in-Situ Ophthalmic Gel of Brimonidine Tartarate

Purpose: Conventional ophthalmic drops suffer from poor bioavailability (<5%) due to rapid precorneal drainage and lacrimation. This study aims to develop and optimize an ion-activated in-situ ophthalmic hydrogel containing Brimonidine Tartrate to enhance precorneal residence time and improve therapeutic efficacy for open-angle glaucoma. Methods: Gellan gum (0.6% w/v) was selected as the ion-activated phase-transition polymer. Formulations were adjusted for isotonicity using boric acid and preserved with phenylmercuric nitrate. Disodium edetate (0.05% w/v) was incorporated to prevent drug crystallization under freeze-thaw conditions. Polyethylene glycol 400 (PEG 400) was added at various levels (0.1%, 0.5%, and 1.0% w/v) as a permeation enhancer. The optimized formulation (F5) was evaluated for clarity, pH, drug content, rheological properties, in-vitro drug release, ex-vivo transcorneal permeation, isotonicity, and ocular irritation using the HET-CAM test. Results: The optimized batch (F5) containing 0.5% PEG 400 was clear, isotonic, maintained a pH of 7.4, and demonstrated immediate gelation upon contact with simulated lacrimal fluid (SLF). Rheological testing showed pseudoplastic behavior, with a 6-fold viscosity increase from sol (55 cps) to gel (325 cps). In-vitro drug release reached 94.4% within 8 hours. Ex-vivo transcorneal permeation studies using goat corneas showed significantly higher sustained permeation (79.3%) compared to a commercial eye ointment (65.8%) over 7 hours. The HET-CAM test yielded an irritation score of 0, confirming it is non-irritant. Conclusion: The developed ion-activated in-situ gelling system represents a highly effective, non-irritating alternative to conventional topical vehicles, successfully prolonging precorneal retention and increasing ocular drug bioavailability.