title: Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion.
abstract: Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors EHS, Eeland Eadwhich account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While EHSand Eelare close to 1, Ead>>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, De, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=De×Eadallowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.
authors: Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal; IDMEC, Departmento de Engenharia Mecânica, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: A F R
authors: AFR
authors: Pimenta
authors: Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: J
authors: J
authors: Ascenso
authors: Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: J C S
authors: JCS
authors: Fernandes
authors: IDMEC, Departmento de Engenharia Mecânica, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: R
authors: R
authors: Colaço
authors: Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal; Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal.
authors: A P
authors: AP
authors: Serro
authors: Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address: b.saramago@tecnico.ulisboa.pt.
authors: B
authors: B
authors: Saramago
mesh_terms: D000327:Adsorption; D002710:Chlorhexidine / Q000737:chemistry; D003261:Contact Lenses; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004008:Diclofenac / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012828:Silicones / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D008689:Methacrylates; D004364:Pharmaceutical Preparations; D011108:Polymers; D012828:Silicones; D014867:Water; D004008:Diclofenac; C005044:hydroxyethyl methacrylate; D002710:Chlorhexidine
keywords: 3-Tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate (PubChem CID: 123371); Chlorhexidine diacetate monohydrate (PubChem CID: 9562059); Contact lens; Diclofenac sodium (PubChem CID: 5018304); Diffusion coefficient; Drug release; Hydrogel membrane; Levofloxacin (PubChem CID: 149096); Partition coefficient; Poly(vinylpyrrolidone) (PubChem CID: 6917); Poly-hydroxyethylmethacrylate (PubChem CID: 13360)