A novel and oral colon targeted isoliquiritigenin delivery system: Development, optimization, characterization and in vitro evaluation

Abstract

The aims of the study were to prepare oral colon targeted gel beads loaded with isoliquiritigenin (ISL) which exhibited a variety of biological activities with a low solubility and oral bioavailability. ISL loaded sodium alginate and pectin gel beads (SA-P gel beads) were prepared by ionic gel technique, and Uniform Design method was used to optimize the formulation. To decrease the leakage in simulated gastric juice and simulated intestinal juice, the Eudragit S-100, sodium alginate and pectin gel beads (EU-SA-P gel beads) were prepared based on the SA-P gel beads. The EU-SA-P gel beads were characterized for size, shape, morphology, encapsulation efficiency, drug loading percentage, swelling degree and in vitro release. The size and shape results showed that the EU-SA-P gel beads were yellow and spherical with a size of 1.22 ± 0.19 mm, and a roundness degree of 72.78% ± 8.25%. It could be confirmed by DSC and FTIR analysis that the drug was not chemically modified but physically dispersed in the gel beads. The swelling degree of EU-SA-P gel beads in simulated gastric juice was 1.13 ± 0.14 at 3 h and remained almost unchanged until 6 h indicating the beads would not dissolve in simulated gastric juice. In simulated intestinal juice, the swelling degree reached the maximum (22.73 ± 3.27) at 3 h which was 20.11 times of that in simulated gastric juice and decreased to 1.85 ± 0.19 at 6 h indicating the gel beads swelled in simulated intestinal juice. As for in simulated colonic juice, the maximum swelling degree was 16.63 ± 3.52 at 3 h which was 0.73 times of that in simulated intestinal juice, then the swelling degree decreased to 1.93 ± 2.33 at 6 h indicating the beads dissolved in simulated colonic juice. The results of in vitro evaluation tests revealed that the cumulative drug release percentage of EU-SA-P gel beads exposure to simulated gastric juice and simulated intestinal juice was only 12.74% ± 3.55% for 5 h. However, the cumulative drug release percentage in simulated colonic juice was 50.64% ± 2.22% from 5 h to 12 h which was 3.97 times of that in pre-colon. These results revealed that the EU-SA-P gel beads was a promising isoliquiritigenin delivery system for colon targeting.