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 3 2 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 (Rel 24 , first order rate constant (K 1 ) and time taken for 50% of the drug release (t 50 ) 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 24 , K 1 , and t 50 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.