Nanoemulsion based in-situ Gel for Ocular Delivery of Brimonidine Tartrate

Background: Brimonidine tartrate is currently used to treat glaucoma; however, conventional ocular formulations have some disadvantages in terms of treating disorders like glaucoma, as less than 5% of the drug reaches a posterior segment of the eye; hence, there is a need for sustained treatment. Objective: The objective of this study was to develop a self-nanoemulsion (SNEDDS) in-situ gel of brimonidine tartrate to investigate the sustained-release effect to improve ocular bioavailability. Methods: Oil, surfactant, and co-surfactant were screened using the pseudo-ternary phase diagram (TPD) by aqueous-titration method based on the drug solubility. Nanoemulsions were evaluated for the pH, viscosity, % drug content, % transmittance, dispersibility, particle size, zeta-potential, TEM, and conductivity test. Nanoemulsion was incorporated into in-situ gel and evaluated for gelling capacity, pourability, gel strength, in vitro drug release study, and drug release kinetics. Results: Castor oil (10%) as oil phase, Acrysol K-140 (10%) as surfactant, and PEG 400 (20%) as co-surfactant were selected in preparation of SNEDDS from TPD. Evaluation parameters of SNEDDS were found in an acceptable range. % Drug release showed the controlled release up to 8 hrs. Optimum % drug content and % CDR were 100.25% and 92.46% after 12hrs, respectively. Optimized SNEDDS in-situ gel followed the Higuchi model via diffusion mechanism having 0.99 R-2 value and exhibiting sustained release up to 12 hr. Stability study proved no significant changes during storage. In vitro, the ocular irritancy test proved suitable for ocular delivery. Conclusion: A sustained-release formulation was obtained by developing brimonidine tartrate SNEDDS in-situ gel as a stable formulation without irritancy during ocular administration.