Supercritical loading of gatifloxacin into hydrophobic foldable intraocular lenses - Process control and optimization by following in situ CO2 sorption and polymer swelling

Abstract

The supercritical impregnation process was used as a green technology for the elaboration of drug delivery intraocular lenses to mitigate the risk of post-operatory endophthalmitis after cataract surgery. Commercially available hydrophobic acrylic (copolymer of benzyl methacrylate and methyl methacrylate) intraocular lenses (IOLs) were impregnated with gatifloxacin, a fourth generation fluoroquinolone drug, using pure supercritical CO₂ (scCO₂) to obtain solvent-free loaded implants. The interaction phenomena involved in the supercritical impregnation were studied by following in situ scCO₂ sorption within the polymer support and the subsequent IOL swelling, and by taking into account drug solubility in the supercritical fluid phase. The drug impregnation yields determined though in-vitro release studies varied between 0.33 and 1.07 ± 0.07 μg·mg^-1_IOL in the studied experimental conditions (8 to 25 MPa, 308 to 328 K and 30 to 240 min impregnation duration). An impregnation duration longer or equal to the time required for a complete CO₂ uptake by the polymer as well as a higher pressure or a higher temperature over the crossover pressure delimiting the upper limit of the retrograde solubility zone, led to higher drug impregnation yields.

Keywords: CO(2) sorption; Endophthalmitis mitigation; Gatifloxacin; In-situ FTIR analyzis; Polymer swelling; Supercritical carbon dioxide (CO(2)) impregnation; Therapeutic intraocular lenses.