Itraconazole Nanocrystals on Hydrogel Contact Lenses via Inkjet Printing: Implications for Ophthalmic Drug Delivery

Abstract

The therapeutic effect of common ocular drug delivery systems is often limited because tear fluid, protective biological barriers, and the blink reflex prevent drugs from reaching their target. Combining nanodrug delivery systems with contact lenses is one approach to increase the precorneal residence time and thus the drug concentration in the eye. Hence, the aim of this study was to selectively print itraconazole (ITZ) nanocrystals on commercially available 1 day soft hydrogel contact lenses using inkjet printing. For this, ITZ nanocrystals stabilized with Poloxamer 407 were prepared and optimized via wet media milling. After careful characterization, the nanocrystals were printed into vials, the printing process was adjusted, and the characteristics of the nanoformulation after printing were investigated. Finally, nanocrystals were printed onto hydrogel contact lenses. By performing a concise design of experiments (DoE), stable nanocrystals with a size of approximately 200 nm, a narrow particle size distribution, a negative surface charge, and an almost spherical shape were obtained. Compared to the bulk material, the apparent solubility was significantly increased and no changes in the solid-state behavior occurred. It was further demonstrated that inkjet printing did not affect the characteristics of the nanocrystals. Multiple layers of the ITZ nanoformulation were printed on soft hydrogel 1 day contact lenses, and a dual drug release profile was obtained in simulated tear fluid. These results clearly show that printing on contact lenses is a promising application for ophthalmic drug delivery.