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Drug loading of foldable commercial intraocular lenses using supercritical impregnation

Bouledjouidja, A, Masmoudi, Y, Sergent, M, Trivedi, Vivek, Meniai, A, Badens, E (2016) Drug loading of foldable commercial intraocular lenses using supercritical impregnation. International Journal of Pharmaceutics, 500 . pp. 85-99. (doi:https://www.sciencedirect.com/science/article/pii/S0378517316300163)

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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 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 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 μgCIP/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 (8.50–14.53 μgDXP/mgIOL). 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.

Item Type: Article
DOI/Identification number: https://www.sciencedirect.com/science/article/pii/S0378517316300163
Uncontrolled keywords: Cataract post-operative treatment, Drug delivery systems, Supercritical impregnation, Foldable P-HEMA intraocular lenses, Response surface methodology, Drug release study
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Central Services > Universities at Medway
Faculties > Sciences > Medway School of Pharmacy
Depositing User: Vivek Trivedi
Date Deposited: 25 Apr 2019 12:07 UTC
Last Modified: 17 Jun 2019 09:51 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/73623 (The current URI for this page, for reference purposes)
Trivedi, Vivek: https://orcid.org/0000-0001-9304-9214
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