Managing allergic conjunctivitis via ophthalmic microemulsions: Formulation, characterization, in vitro irritation studies based on EpiOcular™ eye irritation assay and in vivo studies in rabbit eye

Abstract

The purpose of this work was the development of an alternative ocular tetrahydrozoline hydrochloride (THZ) microemulsion for the management of allergic conjunctivitis. Pseudo-ternary phase diagrams were used to produce the microemulsions. For the formulation of the microemulsions, isopropyl myristate was selected as oil. Furthermore, various surfactants were applied for the determination of their suitability; ME-1 and ME-4 were developed using Sorbitan monolaurate 80 and Polysorbate 80, for ME-2 and ME-5 Sorbitan monolaurate 80 and macrogolglycerol ricinoleate while for ME-3 and ME-6 Sorbitan monolaurate 80 and Polysorbate 20. For ME-1, ME-2, and ME-3 propylene glycol and ethanol, for ME-4, ME-5, and ME-6 ethanol and polyethylene glycol were used as co-surfactants. Various characterization parameters of microemulsions were evaluated such as droplet size, conductivity, zeta potential, viscosity, and pH. In addition, the drug release, stability, sterility, safety, ex vivo, and in vivo experiments were studied. The characterization showed that the formulations can act as suitable carriers for eye application. In addition, it was revealed that microemulsions were found stable and sterile. The formulations released the drug in a sustained manner. Ex vivo diffusion studies exhibited that the microemulsions can be used for topical delivery to the eye. Assessment of in vitro ocular irritation was conducted by an in vivo prediction model, EpiOcular™ eye irritation test. Based on the in vivo studies, the chosen ideal microemulsion showed longer contact time to the cornea than the commercial product. Moreover, the developed ocular carrier was found to be safe from the viewpoint of in vitro ocular irritancy and mutagenicity. In conclusion, according to characterization results, the THZ microemulsions can act as a hopeful approach for topical eye application.