STABILITY AND OCULAR IN-VIVO PHARMACODYNAMIC STUDY OF ION ACTIVATED BRIMONIDINE TARTARATE INSITU GEL

Objective: The goal of this study was to evaluated anti-glaucoma activity of ion-activated in-situ gel of Brimonidine Tartarate (BT) and to predict the shelf of the developed formulation. Method: sol-gel formulation was prepared by using gellan gum as an ion-activated gel-forming polymer, sterculia foetida gum and kappa carragennan as mucoadhesive agent and hydroxy propyl methyl cellulose (HPMC E50LV) as release retardant polymer. Phenyl ethyl alcohol as preservatives in borate buffer. Glaucoma was induced by marginal ear vein using 5% dextrose solution. Schiotz tonometer was use to measure the induced glaucoma. Long terms and accelerated stability studies were carried out. The formulation was characteristics for pH, clarity, sterility, in-vitro gelation studies and drug content by RP-HPLC method. Result: The mean normotensive IOP was in the range of 17.5±0.08 to 19.1±0.40 mm Hg in both the eyes. Glaucoma was induced in the both eye with 5% dextrose solution and the mean IOP in both eyes was in the range of 26.2±0.21 to 29.9±0.25 mm Hg. Student paired Ttest ( F2) vs. Distilled water) was analysed and it was found that there is a highly significant difference between the means. This indicates the test drug is effective in the form of in-situ gels. The repeated measures one –way ANOVA with Tukey's multiple comparison test indicate the data is not significant, i.e p value is greater than p<0.05. In-situ gel are able to control the induced IOP and the IOP values of treated in-situ gel are near to normal IOP reading. Student unpaired and paired T test along with one way ANOVA data shows that there is a marginal significant difference between the means of F1 and F2. With p value of <0.0060 for student unpaired, <0.0050 for student paired T test. There is no significant difference between F2 and normal IOP but there is a marginal significant difference between F1 and normal IOP. Which highlight F2 is better in controlling induced/elevated IOP compared to F1. in-situ gels were translucent, Immediate gelation was formed with in sec, as it was dropped and remained stable. The formulations were free from microorganisms at 30 °C ± 2 °C/65% RH ± 5% RH and at 40°C ± 2°C/75% RH ± 5% RH. The chromatograms were obtained with acceptable tailing factors (<2), not much variation was observed in the retention time. % drug content was found to be in the range of 9 9.46 % to 96% at 40°C ± 2°C/75% RH ± 5% RH by RP-HPLC. The shelf life (t90%) of F2 was found to be 2.5 years at 30 °C ± 2 °C/65% RH ± 5% RH .and at 40°C ± 2°C/75% RH ± 5% RH shelf life (t90%) was found to be 2 years. Conclusion: 5 % dextrose infusion through marginal ear vein is better in inducing IOP. Schiotz tonometer remains the preferred screening instrument. Brimonidine tartarate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. So a synergistic effect can be obtained with help of in-situ gels in order to control elevated intra-ocular pressure in glaucoma. The above study highlights that formulation with sterculia foetida is better compared to kappa carragennan in controlling induced IOP. Key words: Sterculia Foetida gum, marginal ear vein, Schiotz tonometer, Brimonidine Tartarate.