Studies on the design of drug delivery systems for ophthalmic application

Loteprednol etabonate (LE) is a topical corticosteroid used for the treatment of inflammatory conditions of the cornea and anterior segment of the eye and for the reduction of edema. LE, which has low ocular bioavailability, has side effects such as headache, corneal disorder, eye discharge, ocular discomfort and dry eye. Reducing the side effects of LE, increasing its bioavailability and therapeutic properties may be possible with the design of a new dosage form to be developed as an alternative to the traditional topical dosage form. Colloidal nanoparticular systems (SLN, NLC and NE) are advantageous systems for ocular administration of drugs with low water solubility. Since the droplet/particle size is at the nanometer level, they facilitate the passage of drugs through the cornea. These systems are suitable for sterilization and large-scale production. In this study, the experimental design (DoE) of LE and the design of SLN, NLC and NE formulations were made within the scope of quality design (QbD). While Precirol® ATO 5 was used as lipid in SLN and NLC formulations, oleic acid was used for NE and NLC formulations. While the total lipid/fat ratio used in the formulations is 4%, 5%, 6%, 7% and 8%, the most stable formulations are those using 5% Pluronic®F68. Among these formulations, it was determined that the particle size of SLN and NLC was below 100 nm, droplet size of NE was below 150 nm, and showed the highest stability at 5 oC for 180 days. It was determined that the release of the drug from the formulations was in accordance with the Korsmeyer-Peppas release kinetics and was via diffusion according to Fick's 1st Law. The selected formulations were tested by performing an ex vivo permeation study from the cornea excised from the bovine eye, SLN and NLC formulations showed the highest amount of drug detected in the corneal epithelium, while the highest amount of drug detected on the corneal surface was seen in the control group and marketing product. With the formulations developed in this study, it will be possible to increase the bioavailability of LE compared to the suspension form. By reducing the amount of corticosteroid used, an alternative could be offered for anti-inflammatory effect. Key Words: loteprednol etabonate, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion, ophtalmic administration