Interaction of Calcium-Induced Alginate Gel Beads with Propranolol

Abstract

The loading capacity of calcium-induced alginate gel beads for propranolol, selected as a cationic model drug, was investigated with particular attention to the effects of excess Ca2+ in the beads, pH and drug concentration in the bulk solution. The amount of the drug loaded in the excess Ca2+ -washed beads was higher than that in the corresponding unwashed beads. Decreasing the pH from 4 to 1 induced size contraction of the washed beads, for which changes of the fraction of ionized carboxyl groups of the polymer seemed to be responsible, and the pKa value was estimated to be 2.8. The drug loading increased in a sigmoid mode with increasing bulk drug concentration when loaded at pH 3—4. It is especially noteworthy that the dramatic increase of the drug loading was accompanied with abrupt contraction of the beads and transformation from a slightly translucent bead body to whitish beads in the vicinity of the inflexion point, and reached a saturated level that depended on the pH. Such physical appearance changes seemed to be due to the precipitation of the drug-polymer complex in the beads but it did not show crystalline nature. The loading capacity could be controlled by adjusting the pH of the medium, and the precipitated form of the drug possibly acts as a good reservoir for efficient drug release. © 1989, The Pharmaceutical Society of Japan. All rights reserved.