Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

A F R Pimenta; J Ascenso; J C S Fernandes; R Colaço; A P Serro; B Saramago

doi:10.1016/j.ijpharm.2016.10.047

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

Int J Pharm. 2016 Dec 30;515(1-2):467-475. doi: 10.1016/j.ijpharm.2016.10.047. Epub 2016 Oct 24.

Authors

A F R Pimenta¹, J Ascenso², J C S Fernandes², R Colaço³, A P Serro⁴, B Saramago⁵

Affiliations

¹ 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.
² Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
³ IDMEC, Departmento de Engenharia Mecânica, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
⁴ 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.
⁵ Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address: b.saramago@tecnico.ulisboa.pt.

PMID: 27789366
DOI: 10.1016/j.ijpharm.2016.10.047

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 E_HS, E_el and E_ad which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While E_HS and E_el are close to 1, E_ad>>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, D_e, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=D_e×E_ad allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.

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).

MeSH terms

Adsorption
Chlorhexidine / chemistry
Contact Lenses
Delayed-Action Preparations / chemistry*
Diclofenac / chemistry
Diffusion
Drug Delivery Systems / methods
Drug Liberation
Hydrogels / chemistry*
Methacrylates / chemistry
Pharmaceutical Preparations / chemistry*
Polymers / chemistry
Silicones / chemistry
Water / chemistry

Substances

Delayed-Action Preparations
Hydrogels
Methacrylates
Pharmaceutical Preparations
Polymers
Silicones
Water
Diclofenac
hydroxyethyl methacrylate
Chlorhexidine