Dissolution Controlled Drug Release from Agarose Beads

Abstract

A simple method was used for loading ibuprofen or indomethacin into agarose beads to obtain sustained release. Placebo beads were prepared by a dropwise addition of a hot aqueous agarose solution into a beaker of chilled mineral oil and water. Prior to loading, the aqueous component in the beads was replaced by repeated soakings in ethanol. Loading was accomplished at room temperature using ethanolic drug solutions. Upon drying, the beads shrank to about a third of their original size. The surface morphology of dried placebo and loaded beads was studied using electron microscopy. The release time at 37° C and pH 7.5 increased with drug loading and at 50% loading the release time was 4 hours for indomethacin and 6 hours for ibuprofen. Release of chlorpheniramine from dried and swollen beads was examined to elucidate the release mechanism. From dissolution studies it was concluded that the delay due to swelling is less than 10 minutes, chlorpheniramine release from swollen beads was primarily diffusion controlled, and the release mechanism for indomethacin and ibuprofen has three components: i) swelling of the beads, ii) dissolution of crystallized drug, and iii) diffusion of dissolved drug from the beads.