Tailored gatifloxacin Pluronic® F-68-loaded contact lens: Addressing the issue of transmittance and swelling.

Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 µg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.

Plackett-Burman design for screening of critical variables and their effects on the optical transparency and swelling of gatifloxacin-Pluronic-loaded contact lens.

The optical and swelling properties of gatifloxacin-loaded contact lens decrease owing to the precipitation of gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the gatifloxacin precipitates and not limited to sustain the release of gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X1, %w/v), the concentration of Pluronic F68 in the packaging solution (X2, %w/v), the concentration of gatifloxacin incorporated in the monomer solution (X3, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during autoclave (X4, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during extraction (X5, %w/v), the time (stabilization time) after the addition of gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X6, h), the pH of the packaging solution (X7), the temperature of the extracted solution (X8, °C), and the curing time for fabricating the contact lens (X9, min). The gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y1, %), optical transmittances after 7 days of sterilization (Y2, %) and swelling percentages after 7 days of sterilization (Y3, %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y1, Y2, and Y3, respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X1) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X2) improved them through micelle formation. The other variables (X3 to X9) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of gatifloxacin-loaded contact lens.