Improvement of the ocular bioavailability of carteolol by ion pair

Ocular bioavailability after instillation of carteolol was investigated by ion pair formation, taking into consideration a balance between lipophilicity and water solubility. The octanol/ water partition coefficient (PC(O/W)) and the aqueous humor concentration in rabbits after instillation of carteolol containing fatty acids having not more than 6 carbons were measured. The longer carbon chain fatty acid showed the higher PC(O/W) of carteolol. The aqueous humor concentration of carteolol increased with carbon chain length of fatty acid and was clearly correlated with logPC(O/W). The increment of counter ion also increased both the logPC(O/W) and aqueous humor concentration of carteolol. The findings suggested that the transcorneal absorption of carteolol would be designed by coordinating with quality and quantity of counter ions. The area under concentration (AUC) in aqueous humor applied by ion pair formulation containing 2% carteolol with sorbate was 2.6 times higher than that by 2% carteolol ophthalmic solution (control), whereas the AUC applied by 4% carteolol ophthalmic solution was 1.4 times higher. The plasma level after instillation of ion pair formulation was almost the same as that of 2% ophthalmic solution. The ratio of AUC (aqueous humor/ plasma) of ion pair formulation was markedly higher, as compared with those of 2% and 4% ophthalmic solution. These results showed that the ion pair formation with sorbate improved the ocular bioavailability of carteolol without enhancing systemic absorption.