Mucoadhesive Properties of Chitosan-Coated Ophthalmic Lipid Emulsion Containing Indomethacin in Tear Fluid

Abstract

To evaluate the residence of chitosan-coated emulsion (CE) containing indomethacin in tears, the drug retention of CE in tear fluid was compared with non-coated emulsion (NE) after instillation in rabbit eyes. CE had mean concentrations 3.6-fold and 3.8-fold higher than NE at 0.5 h and 0.75 h after instillation, respectively. Mean residence time and half-life of CE were lengthened to 1.5-fold and 1.8-fold those of NE, respectively. Volume of distribution of CE in tear fluid was also 1.6-fold greater than that of NE. These findings indicated that retention of the drug in tears was appreciably prolonged by chitosan-coated emulsion, and that CE had higher distribution on the ocular surface than NE. The drug levels in cornea, conjunctiva, and aqueous humor at 1 h after instillation were clearly higher than those of NE. In a generalized ocular pharmacokinetic model, the ratio of CE to NE for peak concentration values (C(max)) and the area under the concentration/time curve (AUC) nearly corresponded to aqueous humor levels in vivo. Additionally, tensile testing showed that the force of detachment between CE and mucin was significantly larger than that of emulsion containing hydroxypropylmethyl cellulose (HPMCE) with a viscosity similar to CE; the forces of detachment of CE and HPMCE measured using phosphate-buffered saline (PBS) were almost the same since these formulations have similar viscosity. Mucoadhesive strength of CE was confirmed by measurements of force of detachment between formulations and mucin. The residence time of the emulsion in tear fluid was prolonged by chitosan coating because of its mucoadhesive properties.