Swelling and dissolution kinetics during peptide release from erodible anionic gel beads.
The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp2-D-Phe5]GHRP, from erodible, non-cross-linked poly(methyl methacrylate-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 erodible 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.
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
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Lee
D000595:Amino Acid Sequence; D000838:Anions; D002021:Buffers; D004058:Diffusion; D005079:Excipients; D005782:Gels; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008863:Microspheres; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000838:Anions; D002021:Buffers; D005079:Excipients; D005782:Gels; D009842:Oligopeptides; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C041048:growth hormone releasing hexapeptide; D013007:Growth Hormone-Releasing Hormone