Formulation Development and Evaluation of Opthelmic IN SITU Gelling Systems of TIMOLOL MALEATE

Abstract

he present investigation is aimed to develop and evaluate safe, effective, newlineand stable ophthalmic stimuli-responsive in-situ hydrogel using the newlinecombination of ion-responsive polymer gellan gum and pH-sensitive polymer newlinecarbopol 934P and the microemulsion (ME) based phase transition\liquid newlinecrystalline (LC) in-situ ocular gelling system for delivery of Timolol maleate in newlinethe treatment of glaucoma. newlineThe selected model drug Timolol maleate (TM) belongs to BCS class I and is newlinethe first line treatment in open angle glaucoma. The drug gets rapid precorneal newlineelimination from conventional formulation. The present study newlineaddresses this issue with two formulation development strategies i.e., stimuliresponsive newlinein-situ gelling system and ME based LC in-situ gelling system. newlineThe present study explores development of stimuli-responsive in-situ gelling newlinesystem with the combined use of ion sensitive gellan gum and pH newlinesensitive/muco-adhesive Carbopol. It is the first attempt of development of newlineocular drug delivery system using gellan gum and carbopol combination by newlineexperimental design. We have used Box-Behnken design to statistically newlineoptimize the formulation parameters and evaluate the effects of formulation newlineattributes, namely concentration of gellan gum, the concentration of carbopol newline934P and concentration of benzododecenium bromide on selected critical newlinequality attributes. Trial run data were analysed using the polynomial equation newlineand response surface plots. Optimized formulation was selected based on newlinedesirability function, design space. The cross-linking between carbopol 934P newlinewith gellan gum in the formation showed more viscous gelling at the newlinephysiological condition to provide long pre-corneal residence time. Trial runs newlineshowed controlled drug release with diffusion-controlled mechanism and good newlinemucoadhesive strength. The preservative benzododecenium bromide showed newlinethe ability to enhance trans-corneal permeation. The optimized formulation newlineselected based on design space has appeared as a clear solution at the nonvii newlinephysiological condition