Drug loading of foldable commercial intraocular lenses using supercritical impregnation

• Published in: International journal of pharmaceutics Vol. 500; no. 1-2; pp. 85 - 99
• Main Authors: Bouledjouidja, A., Masmoudi, Y., Sergent, M., Trivedi, V., Meniai, A., Badens, E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.03.2016; Elsevier
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Inflammatory Agents - chemistry; Carbon Dioxide - chemistry; Cataract post-operative treatment; Ciprofloxacin - chemistry; Dexamethasone - analogs & derivatives; Dexamethasone - chemistry; Drug Delivery Systems; Drug Liberation; Drug release study; Engineering Sciences; Foldable P-HEMA intraocular lenses; Lenses, Intraocular; Methacrylates - chemistry; Pressure; Response surface methodology; Supercritical impregnation; Technology, Pharmaceutical; Drug delivery systems; Ciprofloxacin (PubChem CID: 2764); Monobasic potassium phosphate (PubChem CID: 516951); Foldable P-HEMA intraocular lenses; Response surface methodology; Supercritical impregnation; Poly (2-hydroxyethyl methacrylate) (PubChem CID: 13360); Drug release study; Cataract post-operative treatment; Carbon dioxide (PubChem CID: 280); Disodium hydrogenophosphate (PubChem CID: 24203); Dexamethasone 21-phosphate disodium (PubChem CID: 16961); Ethanol (PubChem CID: 702)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.01.016

[Display omitted] •Preparation of therapeutic drug loaded intraocular lenses (IOLs).•Supercritical impregnation of foldable IOLs with drug components in order to combine cataract surgery and postoperative treatment in single procedure.•Foaming phenomena avoided by coupling slow pressurization and depressurization phases.•Deep and reproducible impregnations.•A prolonged drug release profile. 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 showdeep 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 200bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0D and +21.0D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5mol%) produced impregnation yields comparable to those obtained at 200bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80–200bar) and the impregnation duration (30–240min). CIP impregnation yields ranging between 0.92 and 3.83μgCIP/mgIOL 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 (8.50–14.53μgDXP/mgIOL). Furthermore, unlike CIP, highest DXP impregnation yields were obtained in the presence of ethanol as a co-solvent (5mol%). NMR spectroscopy was performed to confirm complete removal of ethanol in the co-solvent-treated IOLs.