Biphasic release characteristics of dual drug-loaded alginate beads.
The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl2 solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329 microns. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.
Lee
B J
BJ
Biological Rhythm and Controlled Release Lab., College of Pharmacy, Kangwon National University, Chuncheon, Korea.
Cui
J H
JH
Kim
T W
TW
Heo
M Y
MY
Kim
C K
CK
D000464:Alginates / Q000008:administration & dosage* / Q000032:analysis; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008863:Microspheres
D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020723:Glucuronic Acid