Development of optimized mucoadhesive thermosensitive pluronic based in situ gel for controlled delivery of Latanoprost: Antiglaucoma efficacy and stability approaches

Abstract

This work was investigated to formulate an optimized in situ gel of Latanoprost depending on a sol-to-gel transition system upon ocular instillation. The in situ gelling system could overcome the lachrymal drainage, low corneal permeability, poor availability and low therapeutic efficiency revealed by the conventional ophthalmic preparations. An optimal factorial design was built to study the impact of four factors (P127 concentration, P68 concentration, grade and concentration of HPMC) on the temperature of sol-gel transition, mucoadhesion properties and strength of the gel. The prepared formulations were also evaluated for viscosity, pH, in vitro drug release, ex vivo permeability. Stability studies were carried out for the selected formula at different temperatures (4 °C, 25 °C and 35 °C). The anti-glaucoma efficiency of the optimized formula was estimated using an induced glaucoma model in rabbits. The optimum formula revealed sol-gel temperature of 34.3 °C, gel strength of 23.13 g, mucoadhesionof 0.06 m J and high flux of 11.4 μg/cm2/hr. The anti-glucoma efficiency of the in situ gel formulation was 2.9 fold increase compared to eye drop. It also revealed a rapid decrease in Intraocular Pressure (IOP) within 30 min after administration that extended to 8 h compared to the conventional eye drop which showed gradual decrease in IOP that extended for only 3 h. Latanoprost loaded in situ gelling system is more stable at the different temperatures than the traditional eye drop. This developed Latanoprost thermosensitive in situ gel may provide a non-invasive alternative to the conventional anti-glaucoma eye drop.