Dynamic structure model of polyelectrolyte complex based controlled-release matrix tablets visualized by synchrotron radiation micro-computed tomography.

Abstract

Hydrophilic matrix tablets are the most commonly used dosage forms to fabricate oral controlled-release systems. It is highly desirable to design delivery system with novel mechanism to achieve sustained drug release through a simplified preparation process. The chitosan-anionic polymers based matrix tablets is assumed to produce self-assembly in the gastrointestinal tract, then transferring into film-coated tablets from original matrix type. But its dynamic behavior during dissolution process and the on-going internal microstructural changes during drug release were still in the dark. In this study, by using synchrotron radiation X-ray micro-tomography (SR-μCT) with phase contrast imaging, the micro-structure characteristics of chitosan-λ-carrageenan (CS-λ-CG) matrix based tablets during the dissolution were successfully elucidated for the first time. The qualitative and quantitative analyses of intensity distribution distinguished a hydrated CS-λ-CG layer from a solid core. Visualization based on 3D models provided quantitative details on the micro-structural characteristics of hydration dynamics. After CS-λ-CG matrix tablets were immersed in simulated gastric fluid (SGF) pH1.2 medium for 0.5-2.0h, the hydrated layer transformed into a gel layer and a solid swollen layer. The erosion front, swelling front, and solvent penetration front were also defined from the distinguishable micro-structures. More importantly, once the matrix tablet was transferred from SGF to the simulated intestinal fluid (SIF) pH6.8 medium, a new layer with the enhanced strength and compactness in comparison to common gels was formed on the surface of tablets. The temporal and spatial variation of 3D models further provided direct evidence for this cross-linking behavior, the new layer was composed of CS-λ-CG polyelectrolyte complexes (PEC) which subsequently dominated release mechanisms. In summary, the phase contrast SR-μCT technique was utilized to investigate the hydration dynamics of CS-λ-CG matrix tablets which was supposed to provide a novel drug release mechanism. Based on the structure feature obtained from the high contrast image, different hydration region was distinguished and the cross-linked film was identified and visualized directly for the first time.