"3D channel maze" to control drug release from multiple unit tablets.

Abstract

Diffusion is defined as general mechanism for drug release from advanced delivery systems, yet dynamic structure of dosage form intrinsically plays an unknown role. The synchrotron radiation X-ray micro-computed tomography (SR-μCT) three-dimensional (3D) imaging and in-depth analysis of 3D structures were applied to readily differentiate materials and accurately capture internal structure changes of multiple unit pellet system (MUPS) and the constituent pellets, visualizing internal 3D structure of a MUPS of theophylline tablets for their 3 levels hierarchy structures: pellets with rapid drug release characteristics, a protective cushion layer and a matrix layer. Drug release pathways were extracted from SR-μCT images and a 3D maze network was constructed using pore network analysis to quantify the internal structural evolution during drug release. In the initial stage of dissolution about 1h, theophylline release from the MUPS is dominated by diffusion from the matrix layer, whilst the second phase of 23h constant release kinetics is dominated by a 3D channel maze architecture with outlets/channels connecting pellets in the remains of the MUPS, which forms the 3D channel maze as pore networks. The random walking of the dissolved theophylline molecules retarded by the tortuous 3D channel maze which led to the observed controlled release profile as a whole. Based on SR-μCT investigations and 3D structure analysis, a new approach to control drug release via a 3D channel maze structure was discovered.