Design, development, and in vivo characterization of ocular pH-based in situ thixotropic gelling system for the therapy of Glaucoma.

Glaucoma is a condition characterized by increased intraocular pressure of aqueous humor in the anterior segment of the eye, ultimately leading to blindness. The objective of this work was to formulate a preservative-free single-dose topical thixotropic in situ gel loaded with Ripasudil hydrochloride hydrate, a Rho kinase (ROCK) inhibitor that enhances conventional aqueous outflow via the trabecular meshwork and Schlemm's canal. Two independent variables, i.e., chitosan and HPMC E4M, were selected to design nine formulations using a 22 Central Composite Design, which were evaluated for dependent variables, including pH, gelation time, and drug content. Based on desirability outcomes, an optimized formulation was developed and evaluated. At physiological pH, the prepared formulation rapidly transformed into a gel. The optimized formulation demonstrated an average pH, drug content, and gelation time of 5.8 ± 0.1, 99.08 % ± 0.75, and 92.76 s ± 0.14, respectively. The in vitro release of the optimized formulation was found to be 96.82 % in 25 min, while the enhancement ratio demonstrated a 1.86-fold increase in drug permeation. A significant reduction in the intraocular pressure was observed in diseased BALB/c mice. The findings confirmed the safe and stable nature of the developed formulation; however, it warrants further investigation via pharmacokinetics studies and clinical trials.