Preparation and evaluation in vitro of solutions and o/w microemulsions containing levobunolol as ion-pair

Abstract

Aqueous and aqueous-PEG 200 solutions, and o/w microemulsions containing levobunolol (LB) coupled to octanoic acid (OA) as lipophilic ion-pair were submitted to a preliminary investigation in vitro, in view of possible ophthalmic applications. Evaluation of the following was carried out: n-octanol/water partition coefficient, permeation through an artificial lipophilic membrane and through hairless mouse skin, isotonicity and eye irritation in albino rabbits. Permeation studies in aqueous and in aqueous-PEG 200 solutions through the artificial membrane indicated a higher apparent lipophilicity of LB-OA with respect to the drug alone. The transport rate of LB-OA through hairless mouse skin was lower from a microemulsion containing 0.5% w/w drug than from a water-PEG 200 solution simulating the continuous phase, thus suggesting a possible reservoir effect of the dispersed phase of the microemulsion. The microemulsion, which was isotonic and non-irritating on rabbit eyes, appears as a potentially interesting ophthalmic vehicle for LB.