Formulation Effects on Ocular Absorption of Brimonidine in Rabbit Eyes

Abstract

Purite™ (stabilized oxychloro complex) and benzalkonium chloride (BAK) are preservatives. We investigated formulation effects on ocular absorption of brimonidine in rabbit eyes. The formulations compared were: Alphagan^® (0.2% brimonidine tartrate/0.005% BAK, pH 6.4), Brimonidine-Purite (0.2% brimonidine tartrate/0.005% Purite™, pH 7.2), and Brimonidine-PF (0.2% brimonidine tartrate, preservative-free (PF), pH 6.4) solutions. The study was conducted in a cross-over fashion; albino rabbits (n = 18) were given a single 35 μl drop of each test formulation in each eye. Aqueous humor samples were collected at selected times post-dose from subgroups of 2 rabbits per timepoint and analyzed for brimonidine concentrations by LC-MS/MS. The AUC and C_max were calculated. The results showed rapid ocular absorption of brimonidine, with peak concentrations at 0.33-1 hr. The AUC_0-5hr values were 3.78 ± 0.38, 2.77 ± 0.22, and 2.49 ± 0.22 μg-hr/ml (mean ± SEM) for Brimonidine-Purite, Alphagan^® and Brimonidine-PF, respectively. The corresponding C_max values were 2.69 ± 0.72, 1.74 ± 0.13, and 1.24 ± 0.22 μg/ml (mean ± SEM). Brimonidine-Purite provided significantly higher AUC_0-5hr than Alphagan^® (p < 0.05). No statistical significant difference in AUC_0-5hr was found between Alphagan^® and Brimonidine-PF. In conclusion, 0.2% Brimonidine-Purite was 1.4 and 1.5 times more ocularly bioavailable in rabbits than 0.2% Alphagan^® and 0.2% Brimonidine-PF, respectively.