Cyclosporine A is prescribed for a number of ophthalmic applications such as
dry eyes,
uveitis in children and adolescents,
vernal keratoconjunctivitis, and peripheral
ulcerative keratitis. Extended release of
cyclosporine from
contact lenses has been explored due to the significant benefits of increased bioavailability in comparison with
eye drops. Incorporation of
drug loaded particles is considered to be a promising approach for increasing the drug release duration. Here we explore the feasibility of extended release of
cyclosporine and possibly other hydrophobic drugs by dispersing particles that are 100%
drug rather than
drug loaded particles. The expected benefits are high
drug loading and extended release. Specifically, we explore transport of
cyclosporine in
hydroxyethyl methacrylate gels for the case when the gel is loaded with high concentration of
drug leading to in situ formation of particles. We explore whether we can increase the release duration from the
gels by incorporation of the particles, without sacrificing light transmission which is a critical property for
contact lenses.
Hydrogels were prepared by
free radical UV initiated polymerization with
drug dissolved in the monomer
solution at varying loadings. Drug release kinetics were measured from the particle loaded
lenses and fitted to the Higuchi model to determine the diffusivity. The measured diffusivity is two orders of magnitude lower than estimates from Brinkman model. The differences were attributed to the high partition coefficient of about 150, which implies that a majority of the
drug in the gel is bound to the
polymer. The bound
drug can diffuse along the surface or desorb and diffuse. The diffusivity estimates match the measured values after binding is taken into consideration. Light transmittance was measured to determine whether particle incorporation reduces the transparency. Results showed that the drug release duration could be controlled by increasing the
drug loading but the transmittance was significantly reduce particularly at high
drug loadings, which suggest that this approach may have limited applicability for
contact lenses, but could be useful in other applications where light transmission is not critical.