Evaluation of solute diffusion and polymer relaxation in cross-linked hyaluronic acid hydrogels: experimental measurement and relaxation modeling

Evaluation of transport properties of a drug in a hydrogel matrix is of engineering importance in the assessment of drug delivery systems. Water sorption and solute release are the two important aspects that determine the transport of water/solute in a hydrogel. A novel custom-made diffusion cell is used to examine the transport properties in the hydrogels by chemically cross-linking hyaluronic acid in various alkaline solutions at different cross-linker-to-polymer ratios. The tracer diffusion coefficient in the swollen hydrogel matrix in its rubbery state is estimated using a custom-made diffusional cell. The release kinetics is followed at perfect sink conditions, which transform from a glassy polymer dry membrane state to a swollen rubbery gel state. It is shown that the diffusion of solvent (water) through the hydrogel is case II transport, while the diffusion through the swollen hydrogel is case I (Fickian). The diffusion coefficient is proved to be independent of mesh size and pH of the initial solution. However, the release kinetics is influenced by the diffusion of solute and the relaxation of the polymer in hydrogel. The relaxation coefficient is a function of alkalinity in the solution with which the gel is being made. The contribution of relaxation to the transport during solvent sorption and solute release is found to be similar.

Automated summary

Evaluation of transport properties of a drug in a hydrogel matrix is important in drug delivery system assessment. Water sorption and solute release are key factors determining water/solute transport in hydrogels. The diffusion of solvent through the hydrogel is case II transport, while diffusion through the swollen hydrogel is case I (Fickian). The diffusion coefficient is independent of mesh size and pH, but release kinetics are influenced by solute diffusion and polymer relaxation. Relaxation coefficient is affected by alkalinity, showing similar contribution to transport during solvent sorption and solute release.