Formulation and Evaluation of Nanoparticulate In Situ Gel for Ocular Delivery

Abstract

In the present study, novel colloidal nanoparticulate in situ gel of Timolol maleate was investigated for its potential use to improve ophthalmic delivery of the drug. The study was conducted in two steps, first poly lactide co- glycolic acid nanoparticles were prepared and characterized on the basis of particle size, zeta potential and percentage entrapment. And in second step, the drug loaded nanoparticles were dispersed in in situ gel forming solution yielding the nanoparticulate in situ gel. The polymeric nanoparticles were prepared by w/o/w emulsification method. The poly lactide co- glycolic acid nanoparticles were obtained in size range of 189.4-284.9 nm which is considered suitable for ocular delivery without irritation in to eye. The zeta potential of the nanoparticles were obtained in range of -9.6 to -14.5 mV which indicate the stability of nanoparticles. The polydispersivity index of of nanoparticles fond in the range of 0.231-0.491 which indicate the mid range of polydispersivity. The batch E6 was showed smaller particle size 189.4, high zeta potential -14.5 and high entrapment 59.2% as compare to other batches thus selected as optimized formulation for incorporation into in situ gel containing carbopol 934P 1% and HPMC K4M 0.5 % which was showed immediate gelation and optimum viscosity. The mechanism of drug release from nanoparticulate in situ gel was observed to follow higuchi model on the basis of R2 value of mathematical kinetic models. The data obtained in this study thus suggest that nanoparticulate in situ gel of Timolol maleate was successfully designed to give sustained drug delivery.