Swelling and Dissolution Kinetics During Peptide Release from Erodible Anionic Gel Beads

Abstract

The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp²-D-Phe⁵]GHRP, from credible, non-cross-linked poly(methyl methacry-late-co-methacrylic acid) (PMMA/MAA) beads has been investigated at pH 7.4 as a function of buffer concentration. Although the swelling front penetration shows a ionization-limited behavior similar to that of nonerodible cross-linked PMMA/MAA beads, the normalized diameter of the polymer beads exhibits a brief initial rise followed by an extended linear decline due to establishment of the polymer dissolution process. This is consistent with the general kinetic scheme of dissolution of glassy polymers originally predicted for the slab geometry. In all cases, the initial gel thickness increases as a result of the ionization and swelling of the glassy PMMA/MAA beads. This is followed by an extended period of constant gel thickness due to the onset of polymer dissolution and the synchronization of movement of the swelling and dissolution fronts. The resulting constant gel layer thickness as well as the onset and duration of front synchronization shows an increasing trend with decreasing buffer concentrations. As a result, the corresponding peptide release is slower and the release duration longer at lower buffer concentrations. This is believed to be the first time that a synchronization of swelling and dissolution fronts has been documented for a spherical credible sample. Although such synchronization of fronts does not result in a constant rate of peptide release due to the spherical geometry, some non-Fickian release characteristics have been observed.