Development and Characterization of Dual Cross-linked Microbeads for Colon Specific Targeting: Release Kinetic Modeling and Gamma Scintigraphy Studies

Abstract

Objective: The aim of present study is to develop and characterize ionic gelation-based dual Ca2
+ and SO4
2- crosslinked
gel microbeads using blend mixture of biodegradable chitosan and sodium alginate for colon targeting.
Methods: Those diclofenac sodium (DS) loaded microbead formulations were prepared by utilizing ionic
gelation based polyelectrolyte complexes technique that was effectively dual cross-linked with Ca2
+ and SO4
2- ions
containing solutions. Results: The result for surface morphology characterization through scanning electron
microscopy revealed for semispherical and wrinkled shaped rough surfaces of those optimized formulations. The
mean particle size of 761.52–895.22 μm, entrapment efficiency 63.45–78.38% of, and percentage yield of 73.28–
78.69% are resulted, respectively. The swelling degree of those optimized formulations is found with slighter
values into acidic gastric medium (pH = 1.2), whereas increased values into alkaline intestinal mediums (pH = 6.8
and 7.4), respectively, during 4-h time intervals. The experimental vitro release studies revealed for negligible
amount of DS that was released into simulated gastric fluid medium during 2 h, while slower drug released
into simulated intestinal fluid medium during 3 h and augmented released into stem cell factor medium during
18 h studies, respectively. Furthermore, the drug release kinetics modeling studies performed for those optimized
formulations revealed for non-fickian mechanism type that was best fitted with Higuchi and Korsemeyer peppas
mathematical models. These confirmed that drug releases was guided by dual mechanisms of diffusion and
erosion simultaneously. Conclusion: The developed experimental formulations may be used for targeting of DS
into colon and possible management of inflammatory bowel disease, respectively.