Formulation and Development of Environmentally Responsive Ophthalmic In-Situ Gel For Brimonidine Tartrate

摘要

ABSTRACT A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drug being ocularly absorbed. Brimonidine tartrate is an antiglaucomic agent which shows rapid precorneal exclusion and reduced ocular bioavailability when given in form of conventional ophthalmic formulations. The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of in-situ gel forming ophthalmic systems that are instilled as drops into the eye and undergo a sol–gel transition in the cul-de-sac. In the present study, environmentally responsive ophthalmic drug delivery system composed of two gelling polymers with different phase transition mechanisms was developed. Combination of polyacrylic acid (carbopol 934P) and xanthan gum was investigated as ophthalmic vehicle. Different ratios of these polymers were used to prepare environmentally responsive ophthalmic drug delivery system by simple mixing procedure. Developed formulation was assessed for various evaluation parameters such as appearance/clarity, pH, gelation, drug content, rheological measurement, in-vitro release, and sterility testing and stability study. Prepared formulation showed agreeable appearance/clarity, acceptable pH and good gelation property. In-vitro studies demonstrated adequate drug content, desired rheological behaviour and reasonable in-vitro drug release property. Formulation was stable over one month period. In conclusion, the optimum concentration of polymers results in minimized drug loss and sustained drug release. On the basis of these findings, prepared in-situ gel may be considered as a viable alternative to conventional brimonidine tartrate eye drops. Keywords: carbopol 934P, xanthan gum, brimonidine tartrate, antiglaucomic