Biphasic release characteristics of dual drug-loaded alginate beads

Abstract

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.

Alginate in Drug Delivery Systems

“…An interaction between chitosan and the drug molecule was also observed (37,38). Other coatings like Eudragit Õ will also modify the release of drugs from alginate beads (39,40).…”

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

“…Release of the drug from these in situ gel forming systems was characterized by an initial phase of retarded release that became higher on shifting to the intestinal phase. This biphasic pattern of release is a characteristic feature of matrix diffusion kinetics (28). The release efficiency for M1 was 25.56 % in the gastric phase, which increased to reach 71.12 % after 4 h in the intestinal phase expressing dose dumping.…”

Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine after a single oral administration to rats

“…Some scientists suggested that the administration of slow release nifedipine preparations immediately after awakening or in the evening had a favorable effect on the morning blood pressure surge [9,13]. Alternatively, a drug delivery preparation that matches the circadian variations can be designed to control the plasma concentration and pharmacological efficacy [1,3,7,12,14]. The circadian variations on the pharmacokinetics and blood pressure suggests that both the dosing times of nifedipine and the features of the drug delivery system are very important for optimizing drug therapy.…”

“…For these reasons, the dosing time needs to be considered an important parameter affecting the gastrointestinal absorption and bioavailability related to the medical events of various drugs including nifedipine [2,3,[10][11][12][13][14].…”