Characteristics of Drug Release from Gel Beads Formed by Hydrolysis of Alginic Acid into Guluronic Acid Blocks

Abstract

Alginic acid (Alg) is a natural anionic polysaccharide, which consists of α-L-guluronic acid (G) and β-D-mannuronic acid (M). G-G sequence-rich chain regions, known as G-blocks (GB), are important regions for gelation of Alg using divalent cations. In this study, calcium-induced GB gel beads were prepared, and drug release profiles and degradation properties of the GB gel beads were investigated in aqueous media. The GB gel beads swelled slightly in JP XVI 1st fluid (pH 1.2), and only slight release of sodium diclofenac (DF) from the GB gel beads was observed. Disintegration of the GB gel beads was not observed in the 1st fluid. On the other hand, the GB gel beads disintegrated in JP XVI 2nd fluid (pH 6.8), and the rate of disintegration depended on the concentration of calcium chloride used to prepare the GB gel beads. The DF release profiles of the GB gel beads in the 2nd fluid could be controlled by the concentration of CaCl2 used to prepare the GB gel beads. The initial release profile of DF from GB gel beads was not consistent with the profile of disintegration. According to the Higuchi-plot of the percentage of drug content released against the square root of time, gel disintegration did not affect the release of DF from GB gel beads. It appears that a diffusion-type mechanism was responsible for DF release. We propose that the GB gel bead gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.