Development of Ion triggered In-situ gel containing Levofloxacin hemihydrates for ocular delivery: In-vitro and In-vivo evaluation

Abstract

In-situ gelling systems are viscous polymer-based liquids that exhibit sol-to-gel phase transition on the ocular surface due to change in specific physico-chemical parameters like temperature, ionic strength, or pH. A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to pre-corneal loss resulting in only a small fraction of the drug being ocularly absorbed. The effective dose administered can be altered by increasing the retention time of medication into the eye by using in situ gel forming systems, thereby preventing the tear drainage. The aim of the present investigation is to prepare and evaluate novel Ion-triggered ocular gelling systems of Levofloxacin Hemihydrates. These gelling systems involve the use of Sodium alginate as Ion-sensitive polymer and HPMC K4M as viscofying agent. Nine formulations (S1-S9) based on Ion activated In situ gelation using Sodium alginate were preparedwith HPMC K4M  as a common viscolyzer. A 3² full factorial design has been applied with conc. of Sodium alginate and HPMC K4M as independent variables studied at three levels to study their influence on drug release and gelling capacity as dependent variables. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in vitro drug release and in-vivo studies in rabbit eye. The developed formulations showed sustained release of drug for up to 8 hrs. The formulations were found to be non-irritating with no ocular damage.