Abstract
Background: Rebamipide (REB), a mucin secretagogue clinically indicated for dry eye disease, has limited application due to its poor aqueous solubility and low ocular bioavailability. The current study hypothesized that hydrogel contact lenses based on HEMA/NVP could provide prolonged ocular delivery of REB, while amino acids (arginine, lysine, and taurine) and β-cyclodextrin (β-CD) would modulate solubility, release, and corneal permeation of REB. Methods: REB-loaded contact lenses were obtained via soaking. Solubility was measured in phosphate buffer (pH 7.4). In vitro release and ex vivo corneal permeation (sheep cornea) were evaluated using a Franz diffusion cell. Jss, Papp, and cumulative permeation were calculated as permeation parameters. Statistical analyses were performed using linear mixed-effects models (p < 0.05). Results: REB solubility (3.77 mg/mL) was improved by β-CD (4.91–5.28 mg/mL) and amino acids, with the greatest improvement observed with arginine (8.69 mg/mL), followed by lysine (4.80 mg/mL), whereas no effect was observed with taurine. The highest release was observed for arginine-based formulations, followed by lysine, β-CD, and taurine (62.31, 56.98, 56.18, 53.11% at 24 h). In permeation studies, β-CD (1:3) yielded the greatest permeability amongst all formulations (Jss = 0.238 µg/cm²·min; Papp = 1.59 × 10⁻⁴ cm/min; cumulative permeation = 406.27 µg at 24 h), whereas taurine (1:2) exhibited slightly lower permeability than its corresponding formulation but provided a more controlled release profile (Jss = 0.209 µg/cm²·min; cumulative permeation = 384.03 µg). Formulations containing arginine and lysine had higher release but lower permeation. Conclusion: Taurine (1:2) provided the best balance between rate and corneal permeation, achieving predefined performance goals. This system permits the delivery of ~400 µg REB per lens, highlighting its potential as a sustained ocular drug delivery device.