Development and Characterization of Carbonic Anhydrase Inhibitor Based Ophthalmic Nanoemulsions for Treatment of Ocular Hypertension

Abstract

The objective of present study was to develop a stable ophthalmic nanoemulsion for reducing ocular hypertension using Brinzolamide (BRZ) 10 mg/mL which is therapeutically equivalent to marketed reference drug product. Pre-formulation study was performed to evaluate the compatibility of product with materials which come in contact with the product during manufacturing. Medium Chain Triglyceride was selected as oil phase due to the high solubility of Brinzolamide in it as compared to other oils and Polyoxyl 35 castor Oil and Propylene glycol were used as surfactant and cosurfactant respectively. The construction of nanoemulsion was further optimized by D-optimal mixture design, taking oil, Smix and water as independent variables and droplet size and drug entrapment as response variables. Mathematical equations and response surface plots were used to correlate the dependent and independent variables. The optimized composition of nanoemulsion was predicted by numerical optimization technique on the basis of the highest desirability value. The predicted optimized nanoemulsion which contained 5% oil, 15% Smix, and 80% water was formulated and evaluated for ophthalmic application. The optimized nanoemulsion formulation showed droplet size (103.03±1.6nm) and drug entrapment in formulation (101.51±0.81% ) which was in close agreement with the predicted value of response variable by the optimization software, i.e. 102.983 nm and 100.038%, respectively. These results confirmed that the D optimal mixture design can be successfully employed for designing and development of nanoemulsion based formulation of Brinzolamide. Compatibility study was carried out with metal, silicon tubes, filters and plastic containers. Thermal cycling and Photostability study were also performed to ensure the stability of the product. Compatibility study results indicate that drug product was compatible with the product contact materials. Thermal cycling and photostabilty data indicates that there was no significant degradation in the formulation. newline