Design of ocular inserts of brimonidine tartrate by response surface methodology

Reservoir-type ocular inserts of brimonidine tartrate have been formulated by solvent casting technique for once a day administration. The drug-loaded core film was produced by casting a hydroalcoholic solution of hydroxyl propyl methyl cellulose (HPMC) (5% w/v) and glycerin (40% w/w). A 32 factorial design was employed to fabricate the rate-controlling membranes of cellulose acetate butyrate (CAB) using polyethylene glycol-600 (PEG-600) as plasticizer. The effect of CAB and PEG-600 concentrations in the polymeric solutions prior to casting on the drug release at 24 h (Rel24, first order rate constant (K1) and time taken for 50% of the drug release (t50) were evaluated using the F-test. Mathematical models generated using multiple linear regression analysis (MLRA) and analysis of variance (ANOVA) indicated that both the formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization procedure using the desirability approach was used to develop an optimized formulation and thereby validate the mathematical models generated. The experimental values of Rel24, K1, and t50 for the optimized formulation were found to be 75.88 ± 1.14%, 0.067 ± 0.001 (h- 1), 10.30 ± 0.21 h, respectively. The close agreement of the experimental and the predicted values proved the validity and the robustness of the mathematical models generated. A good correlation between the in vitro and the in vivo release data was observed when the optimized formulation was evaluated in a rabbit model.