Phase Transition Microemulsion of Brimonidine Tartrate for Glaucoma Therapy: Preparation, Characterization and Pharmacodynamic Study

Abstract

ABSTRACT Purpose: The aim of this study was to formulate brimonidine tartrate loaded phase transition microemulsions (PMEs), which undergo phase transition from water in oil (W/O) microemulsions to liquid crystalline (LC) and then oil in water (O/W) microemulsions after instilled into the eye and prolong the precorneal residence time and ocular bioavailability for the effective treatment of glaucoma. Methods: The pseudo-ternary phase diagram was developed and various PMEs were prepared using Tween 80 and Span 80 with isopropyl myristate and water. Globule size and shape, physicochemical parameters, in vitro and ex vivo drug release of PMEs were studied. The in vivo anti-glaucoma efficacy of optimized PMEs was studied in an experimental rabbit eyes model and compared with marketed formulation (MF). Results: Globule size of PMEs was found less than 200 nm, which was confirmed by both dynamic light scattering technique and Transmission Electron Microscopy. Physicochemical properties such as pH, refractive index, percentage transparency, viscosity and conductivity were also found in the acceptable ranges. In vitro release studies of PMEs exhibited sustained release property. Ex vivo permeation study also supported the enhanced drug flux through cornea from PMEs as compared with MF. In pharmacodynamic study, a greater reduction in intraocular pressure was seen in PMEs as compared to MF. Conclusion: PMEs as ocular drug delivery system offer a promising approach to enhance the corneal contact, higher permeation and prolonged precorneal retention time in the eye leading to sustained drug release, enhanced bioavailability and patient compliance.