Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation

Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (NevanacA (R)). This study utilized hydroxypropyl-beta-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of NevanacA (R)) and pig eye trans-corneal permeation was studied versus NevanacA (R). Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and NevanacA (R). Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than NevanacA (R). Furthermore, the solution had 11 times higher corneal retention than NevanacA (R). Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by NevanacA (R). The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or NevanacA (R).