title: Drug loading of foldable commercial intraocular lenses using supercritical impregnation.
abstract: The drug delivery through intraocular lenses (IOLs) allows the combination of cataract surgery act and postoperative treatment in a single procedure. In order to prepare such systems, "clean" supercritical CO2 processes are studied for loading commercial IOLs with ophthalmic drugs. Ciprofloxacin (CIP, an antibiotic) and dexamethasone 21-phosphate disodium (DXP, an anti-inflammatory drug) were impregnated into foldable IOLs made from poly-2-hydroxyethyl methacrylate (P-HEMA). A first pre-treatment step was conducted in order to remove absorbed conditioning physiological solution. Supercritical impregnations were then performed by varying the experimental conditions. In order to obtain transparent IOLs and avoid the appearance of undesirable foaming, it was necessary to couple slow pressurization and depressurization phases during supercritical treatments. The impregnation yields were determined through drug release studies. For both drugs, release studies show deep and reproducible impregnation for different diopters. For the system P-HEMA/CIP, a series of impregnations was performed to delimit the experimental range at two pressures (80 and 200 bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0 D and +21.0 D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5 mol%) produced impregnation yields comparable to those obtained at 200 bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0 D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80-200 bar) and the impregnation duration (30-240 min). CIP impregnation yields ranging between 0.92 and 3.83 μg CIP/mg IOL were obtained from these experiments and response surface indicated the pressure as a key factor in the process. The DXP impregnation in P-HEMA was higher than CIP at all the tested conditions (8.50-14.53 μg DXP/mg IOL). Furthermore, unlike CIP, highest DXP impregnation yields were obtained in the presence of ethanol as a co-solvent (5 mol%). NMR spectroscopy was performed to confirm complete removal of ethanol in the co-solvent-treated IOLs.
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13454 Aix-en-Provence, France. Electronic address: abir.gch@hotmail.fr.
authors.forename: A
authors.initials: A
authors.lastname: Bouledjouidja
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13454 Aix-en-Provence, France. Electronic address: yasmine.masmoudi@univ-amu.fr.
authors.forename: Y
authors.initials: Y
authors.lastname: Masmoudi
authors.affiliation: Laboratoire d'Instrumentation et de Sciences Analytiques (EA 4672), Aix Marseille Université Avenue Escadrille Normandie Niemen, 13397 Marseille Cedex 20, France.
authors.forename: M
authors.initials: M
authors.lastname: Sergent
authors.affiliation: University of Greenwich, Faculty of Engineering and Science, Central Avenue, Chatam Martime, Kent ME4 4TB, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Trivedi
authors.affiliation: Laboratoire de l'Ingénierie des Procédés de l'Environnement, Université Constantine 3, Algeria.
authors.forename: A
authors.initials: A
authors.lastname: Meniai
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13454 Aix-en-Provence, France. Electronic address: elisabeth.badens@univ-amu.fr.
authors.forename: E
authors.initials: E
authors.lastname: Badens
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D002939:Ciprofloxacin / Q000737:chemistry; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D007910:Lenses, Intraocular; D008689:Methacrylates / Q000737:chemistry; D011312:Pressure; D013678:Technology, Pharmaceutical
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D008689:Methacrylates; D002245:Carbon Dioxide; C004180:dexamethasone 21-phosphate; D002939:Ciprofloxacin; C005044:hydroxyethyl methacrylate; D003907:Dexamethasone
keywords: Carbon dioxide (PubChem CID: 280); Cataract post-operative treatment; Ciprofloxacin (PubChem CID: 2764); Dexamethasone 21-phosphate disodium (PubChem CID: 16961); Disodium hydrogenophosphate (PubChem CID: 24203); Drug delivery systems; Drug release study; Ethanol (PubChem CID: 702); Foldable P-HEMA intraocular lenses; Monobasic potassium phosphate (PubChem CID: 516951); Poly (2-hydroxyethyl methacrylate) (PubChem CID: 13360); Response surface methodology; Supercritical impregnation