Proposal of a New in vitro Evaluation Method Using pH Changes as an Indicator to Evaluate Irritation by Ophthalmic Solutions

We proposed an in vitro test based on pH changes in ophthalmic solutions with the addition of lacrimal buffer, and examined anti-allergic ophthalmic solutions (acitazanolast hydrate, amlexanox, epinastine hydrochloride, ketotifen fumarate, levocabastine hydrochloride, olopatadine hydrochloride, pemirolast potassium, sodium cromoglycate, and tranilast) and anti-glaucoma ophthalmic solutions (brimonidine tartrate, carteolol hydrochloride, dorzolamide hydrochloride, isopropyl unoprostone, pilocarpine hydrochloride, timolol maleate, and travoprost) by using the in vitro test. Resistance to the lacrimal buffer capacity of ketotifen ophthalmic solution was higher than that of the other anti-allergic ophthalmic solutions tested. Among anti-glaucoma ophthalmic solutions, resistance to the lacrimal buffer capacity of the isopropyl unoprostone and dorzolamide ophthalmic solutions was higher than that of the other ophthalmic solutions tested. We also found relationships between ophthalmic additives and the pH-buffering effect in ophthalmic solutions, and demonstrated that D-mannitol, which is an ophthalmic additive, resisted the pH-buffering effect in artificial tears. Furthermore, high resistance was observed to the lacrimal buffer capacities of ophthalmic solutions with D-mannitol. These results will contribute to further studies aimed at reducing irritation caused by ophthalmic solutions.