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

On the ability of chromatographic mass balance to predict solute diffusivity in drug delivery systems

“…Several systems from literature were analyzed to prove model reliability and hypothesis coherence by comparing simulation results with experimental data. 27,28,[33][34][35] This represents the validation with literature data of the joint between chromatography and drug delivery that could pave the way for a better design of these medical devices. Figure F2 2, the two cases of drugs with notendency to aggregate (nonaggregative drugs) or to form dimers or trimers (aggregative drugs) are schematized.…”

Microparticles Formulation as a Targeting Drug Delivery System

“…Two forms of release profiles may be observed in this case: a burst effect if the membrane is saturated with the drug and a time lag if drug has not penetrated the membrane [26][27][28]. A second possible model based on the diffusion mechanism occurs when a partially soluble membrane encloses a drug core.…”

Intra-ocular lens optical changes resulting from the loading of dexamethasone

“…Subsequently, ethyleneglycol dimethacrylate was incorporated in this solution as the crosslinking agent (100 mM), and the mixture was degassed before the addition of 2,20-azobis(2-methylpropionitrile) (AIBN) as the polymerization initiator. Subsequently, the mixture was injected into a rectangular mold, and thermo-polymerization took place at 60 °C for 1 h, resulting in a solid polymer plate with DXM homogeneously dispersed within the matrix [14]. The lenses were machined from this polymer base.…”