Supercritical Drug Impregnation onto Intraocular Lenses

Supercritical impregnation is an attractive “clean” alternative to conventional soaking into liquid process, using generally organic solvents. Impregnation process can be used for the development of controlled delivery systems that can be applied in pharmaceutical and medical fields. This work focuses on the preparation of controlled drug delivery systems for ophthalmic applications through supercritical impregnation. More particularly, commercial intraocular lenses (IOLs) used in cataract surgery are loaded with ciprofloxacin (an antibiotic) and dexamethasone 21-phosphate disodium salt (an anti-inflammatory drug) in order to prevent shortand long-term postoperative complications. Foldable hydrophilic and rigid hydrophobic acrylate IOLS, made respectively from derivative of poly (2-hydroxyethyl methAcrylate) (P-HEMA) and Poly (methyl methAcrylate) PMMA were studied. Supercritical impregnations were carried out in a batch mode and impregnation yields were determined through drug release kinetic studies in a solution simulating the aqueous humor. The influence of operating conditions on impregnation was studied by performing preliminary impregnation experiments followed by experimental designs. Transparent IOLs presenting an effective impregnation were obtained. The highest impregnation yields for DXP and CIP in PMMA IOLs were 18.3 and 2.8 μgdrug /mgIOL respectively and the highest impregnation yields for DXP and CIP in P-HEMA IOLs were 14.5 and 4.1 μgdrug/mgIOL respectively. Those results indicate higher affinity of DXP for PMMA and P-HEMA IOLs than CIP, which was confirmed by partition coefficient values. Despite the low solubility of each drug in the fluid phase, homogeneous and in-depth impregnations were successfully obtained. A prolonged drug delivery during 40 days was obtained for most impregnation experiments (for both kinds of IOLs). Optical characterizations of IOLs were carried out by evaluating the diopter power as well as the imaging quality through the determination of the Modulating Transfer Function at a specified spatial frequency according to European Standard (ISO 11979-2:2014). Results show that optical properties were conserved after supercritical impregnation.