Hydrophobic anionic gel beads for swelling-controlled drug delivery

Abstract

Using oxprenolol HCl as a model drug, the effects of pH and buffer concentration on the swelling and drug release properties in cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads have been investigated. The kinetics of swelling of such hydrophobic anionic gel beads from the dehydrated state appear to be governed primarily by a diffusion-ionization process which becomes more ionization-controlled at higher buffer concentrations. Within the range of ionic compositions studied, the swelling rate increases and the initial swelling/ionization front penetration becomes increasingly linear in time with increasing pH or buffer concentration of the swelling medium. The corresponding swelling bead diameter appears to reach an equilibrium value as soon as the penetrating ionization fronts meet at the center, suggesting a swelling equilibrium in the ionized shell due to rapid mechanical readjustment in the gel phase. At oxprenolol loading levels up to 15%, both the transient drug release and swelling bead diameter exhibit extended quasi-linear regions despite the inherent limitation of decreasing surface area at the penetrating front in the spherical geometry. In addition, both the drug release and the dimensional changes reach completion when the penetrating ionization fronts meet at the center, suggesting a true swelling-controlled drug release behavior.