Probing the mechanisms of drug release from hydrogels

Abstract

The swelling and drug release kinetics in suspension polymerized glassy poly(hydroxyethyl methacrylate/ (PHEMA) beads have been studied in detail using model drugs of both high and low water solubilities: oxprenolol HCl (sol. in H 2O ≈ 77%) and diclofenac sodium (sol. in H 2O ≈ 2.65%). The current results verify our previous findings that the drug loading has a definite effect on the drug release mechanism from hydrogels. The initial swelling front penetration has been observed to behave more Fickian as drug loading increases. Such a transition can be considered as a change of relative importance of the diffusion process versus the polymer relaxation as a function of drug loading. The swelling fronts have also been observed to accelerate near the core. This is shown to be the natural outcome of the associated moving boundary problem in spherical geometry and not, as proposed by some authors, a super-Case II transport behaviour. In all cases, the swelling bead dimension goes through a maximum followed by a gradual approach to an equilibrium value during the drug release. In addition, a doublefront formation (a swelling front and a drug dissolution front) has been observed for diclofenac sodium during the drug release due to the low drug solubility. We have also shown that by considering the increase in hydrogel bead dimension due to swelling and the decrease in dimension due to drug release, the swelling maximum in the transient dimensional changes can be qualitatively predicted. The osmotic contributions due to the presence of the drug can then be estimated from the differences between the experimental and calculated transient dimensional changes.