(269d) A Personalized Approach Towards the Delivery of Itraconazole Nanocrystals Onto Contact Lenses Using Inkjet Printing

Ocular administration of drugs is usually performed via eye drops or ointments. This most often increases the production of tear fluid, which causes the drug to be easily flushed out of the eye, resulting in a very short residence time and consequently low bioavailability. Approaches to extend the residence time include mucoadhesive ophthalmic ointments/films, eye drops that form a viscous gel upon administration, and contact lenses. Drug-loaded contact lenses are of particular interest as they can increase the residence time of drugs from 1-2 min to more than 30 min, which results in a 50% increased ocular bioavailability [1]. A disadvantage, however, is that drug-loaded contact lenses may impair the visibility of patients. A promising method to counteract this problem is inkjet printing. Inkjet printing enables the targeted printing of picoliter droplets onto substrates with high precision, allowing the production of personalized dosage forms [2]. A decisive factor for the printability of the ink solution is the solubility of the drug in the respective solvent. In order to increase the solubility of poorly soluble drugs and thus achieve therapeutic doses, particle size reduction of the bulk material into the nanometer range can be performed. The obtained nano-formulation can then be printed onto the lens in a targeted manner [3].

This study aims at demonstrating the selective printability of a nano-formulation based on the model drug Itraconazole (ITZ) on commercially available soft hydrogel 1-day contact lenses using inkjet printing. First, ITZ nanocrystals were prepared using wet media milling, optimized via Design of Experiments (DoE) and carefully characterized in terms of particle size, shape, solid-state behavior, and saturation solubility. In a second step, the printing process was adjusted regarding optimum firing frequency and pulse shape. Effects of the jetting process on particle size, size distribution, crystallinity and content uniformity were evaluated. Finally, printing trials on contact lenses were conducted.

As a result of DoE analysis and optimization, nanocrystals with a size of approximately 200 nm, a narrow particle size distribution and an almost spherical shape were obtained. Compared to the bulk material, the solubility was significantly increased and no changes in the solid-state behavior occurred. Inkjet printing into vials did not negatively affect the characteristics of the nanocrystals. In addition, multiple layers (i.e., up to 10) could be printed on the contact lenses using the configured ring pattern. The area of the pupil was selectively omitted, thereby avoiding any visual impairment. This highlights that printing on contact lenses is a promising application for ophthalmic drug delivery, allowing personalized dosing without affecting visibility.

REFERENCES

1. F.A. Maulvi, D.T. Desai, K.H. Shetty, D.O. Shah, M.D.P. Willcox, Advances and challenges in the nanoparticles-laden contact lenses for ocular drug delivery, Int. J. Pharm. 608 121090 (2021).
2. W.H. Chou, A. Gamboa, J.O. Morales, Inkjet printing of small molecules, biologics, and nanoparticles, Int. J. Pharm. 600 120462 (2021).
3. W.S. Cheow, T.Y. Kiew, K. Hadinoto, Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs, Eur. J. Pharm. Biopharm. 96 314–321 (2015).